bioluminate user manual

Schrdinger Press

BioLuminate User Manual

BioLuminate 1.6 User Manual

BioLuminate User Manual Copyright 2014 Schrdinger, LLC. All rights reserved.

While care has been taken in the preparation of this publication, Schrdinger

assumes no responsibility for errors or omissions, or for damages resulting from

the use of the information contained herein.

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Desmond is used with the permission of D. E. Shaw Research. All rights reserved.

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software.

August 2014

ContentsDocument Conventions ..................................................................................................... ix

Chapter 1: Introduction ....................................................................................................... 11.1

1.2

1.3

1.4

Chapter 2.1

2.2

2.3BioLuminate 1.6 User Manual iii

Overview of BioLuminate Features........................................................................ 11.1.1 Protein Analysis Tools......................................................................................... 11.1.2 Protein Structure Tools........................................................................................ 21.1.3 Peptide Tools....................................................................................................... 21.1.4 Protein Alignment and Docking Tools ................................................................. 31.1.5 Protein Mutation and Modification Tools ............................................................. 3

1.1.6 Antibody Tools..................................................................................................... 4

Running Schrdinger Software .............................................................................. 4

Starting Jobs from the BioLuminate Interface..................................................... 6

Citing BioLuminate in Publications ....................................................................... 7

2: The BioLuminate Interface ..................................................................... 9 The Main Window ...................................................................................................... 9

Structures and Projects ......................................................................................... 11 The Toggle Table...................................................................................................... 12

2.3.1 Quick Access Buttons ....................................................................................... 122.3.2 Table Rows........................................................................................................ 13

2.3.3 The Action Menu............................................................................................... 142.3.3.1 Changing the View................................................................................. 142.3.3.2 Minimizing the Structure Energy ............................................................. 152.3.3.3 Changing the Appearance of Structures.................................................. 152.3.3.4 Displaying Polar Contacts....................................................................... 162.3.3.5 Generating an Atom Selection ................................................................ 172.3.3.6 Displaying Atoms Related By Crystallographic Symmetry ........................ 182.3.3.7 Modifying an Atom Selection .................................................................. 182.3.3.8 Removing Selections ............................................................................. 202.3.3.9 Renaming Rows .................................................................................... 202.3.3.10 Duplicating Rows ................................................................................. 202.3.3.11 Removing Entries from the Workspace ................................................. 20

Contents

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2.3.3.12 Deleting Entries from the Project .......................................................... 202.3.3.13 Creating Project Entries ....................................................................... 212.3.3.14 Adding and Removing Hydrogens......................................................... 212.3.3.15 Removing Waters ................................................................................ 21

2.4

Chapter 3.1

3.2

3.3

Chapter

Chapter 5.1

5.2

5.3

Chapter

Chapter 7.1

7.2

7.3

7.4r Software Release 2014-3

2.3.3.16 Computing Properties .......................................................................... 212.3.4 The Show Menu................................................................................................ 222.3.5 The Hide Menu ................................................................................................. 232.3.6 The Label Menu ................................................................................................ 24

2.3.7 The Color Menu ................................................................................................ 25

Shortcut Menus ....................................................................................................... 26

3: Analyzing Protein Quality...................................................................... 27 Ramachandran Plot................................................................................................. 27

Protein Report.......................................................................................................... 28

Plot Toolbar .............................................................................................................. 30

4: Analyzing Residue Properties ........................................................... 31

5: Identifying Consensus Molecules ................................................... 35 Choosing the Target Protein ................................................................................. 36

Finding and Aligning Homologs........................................................................... 36

Viewing Consensus Molecules ............................................................................. 37

6: Identifying Reactive Residues ........................................................... 39

7: Predicting Aggregation Regions ...................................................... 43 Creating an Aggregation Surface ......................................................................... 43

Setting Options for Aggregation Surfaces ......................................................... 45

Analyzing the Surface............................................................................................. 45

Using the Results for Mutation Studies .............................................................. 47

Contents

Chapter 8: Analyzing Protein Interface Interactions ..................................... 498.1 Selecting the Interacting Proteins ........................................................................ 50

8.2 Running the Analysis ............................................................................................. 50

8.3

8.4

Chapter

Chapter 10

10

10

Chapter 11

11

11

11

11BioLuminate 1.6 User Manual v

Examining the Results ........................................................................................... 52

Viewing Interaction Properties in the Workspace ............................................. 53

9: Locating Large-Scale Motions........................................................... 55

10: Predicting Peptide Properties ......................................................... 57.1 Alpha Helix Stability.............................................................................................. 57

.2 QSAR from Sequences......................................................................................... 5910.2.1 Loading the Sequences and Properties.......................................................... 6010.2.2 Building a QSAR Model .................................................................................. 6110.2.3 Examining the Model ...................................................................................... 6210.2.4 Applying the Model to Other Sequences ........................................................ 6410.2.5 Setting Options for PLS Methods.................................................................... 64

10.2.5.1 PLS Options ........................................................................................ 6410.2.5.2 KPLS Options ...................................................................................... 65

.3 Peptide Binding to a Receptor ............................................................................ 6710.3.1 Defining the Protein Receptor Region ............................................................ 6710.3.2 Specifying the Peptides to Dock ..................................................................... 6810.3.3 Setting Docking Options ................................................................................. 6910.3.4 Running the Job.............................................................................................. 70

11: Protein-Protein Docking ...................................................................... 71.1 Preparation of Proteins for Docking .................................................................. 72

.2 Docking a Protein to Another Protein................................................................ 72

.3 Applying Constraints............................................................................................ 74

.4 Creating Dimers and Trimers .............................................................................. 75

.5 Docking an Antigen to an Antibody................................................................... 75

Contents

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Chapter 12: Homology Modeling of Proteins .................................................... 77

Chapter 13: Residue and Loop Mutation ............................................................. 8113

13

Chapter 14

14

14

14

14

Chapter 15

15

15r Software Release 2014-3

.1 Residue Mutations ................................................................................................ 8213.1.1 Selecting the Residue to Mutate ..................................................................... 8313.1.2 Defining the Mutation ...................................................................................... 8313.1.3 Refining the Mutated Structure ....................................................................... 84

.2 Insertions, Deletions, and Loop Swaps ............................................................ 8513.2.1 Choosing the Original and Replacement Loop ............................................... 8713.2.2 Editing the Replacement Loop........................................................................ 8813.2.3 Choosing the Output and Method ................................................................... 89

14: Cross-Linking Proteins......................................................................... 91.1 Preparing the Proteins for Cross-Linking......................................................... 91

.2 Picking the Connection Residues ...................................................................... 92

.3 Defining the Linkers.............................................................................................. 94

.4 Choosing Methods and Running the Job ......................................................... 95

.5 Examining the Results ......................................................................................... 95

15: Scanning for Residue Mutations ................................................... 97.1 Selecting and Analyzing the Protein.................................................................. 97

.2 Setting Up and Running the Job ........................................................................ 9815.2.1 Choosing Residues to Mutate......................................................................... 9815.2.2 Choosing the Mutations .................................................................................. 9915.2.3 Setting Optimization Options for Affinity Maturation...................................... 10115.2.4 Choosing Refinement Options ...................................................................... 10215.2.5 Selecting Properties to Calculate.................................................................. 10315.2.6 Running the Job............................................................................................ 103

.3 Using Homologs for Identifying Mutations .................................................... 10415.3.1 Obtaining Homologs from a BLAST Search ................................................. 10415.3.2 Importing Homologs...................................................................................... 105

Contents

15.3.3 Aligning Homologs ........................................................................................ 10515.3.4 Selecting Residues by Homology ................................................................. 10615.3.5 Selecting Residues by Structural Attributes.................................................. 107

15

Chapter 16

16

16

16

16

16

Chapter 17

17BioLuminate 1.6 User Manual vii

15.3.6 Making the Selection..................................................................................... 107

.4 Examining the Mutation Results ...................................................................... 10815.4.1 Binding Affinity Prediction ............................................................................. 11015.4.2 Stability Prediction ........................................................................................ 111

16: Locating Possible Mutations for Disulfide Bridges.......... 113.1 Selecting and Analyzing the Protein................................................................ 113

.2 Choosing Residue Pairs to Mutate................................................................... 115

.3 Relaxing the Structure Around the Mutation Site ......................................... 117

.4 Running the Job .................................................................................................. 117

.5 Examining the Results ....................................................................................... 118

.6 Workflow Summary ............................................................................................. 120

17: Antibody Modeling ................................................................................ 121.1 Modeling an Antibody Structure ...................................................................... 121

17.1.1 Importing the Antibody Sequence................................................................. 12217.1.2 Choosing a Database ................................................................................... 12317.1.3 Selecting the Coordinates for the Framework Region................................... 12417.1.4 Filtering the Database by Property ............................................................... 12517.1.5 Generating the Loop Model .......................................................................... 12717.1.6 Selecting Clusters for a Loop........................................................................ 12817.1.7 Refining Loops .............................................................................................. 13017.1.8 Summary ...................................................................................................... 132

.2 Humanizing Antibodies by Residue Mutation................................................ 13317.2.1 Analyzing the Antibody ................................................................................. 13317.2.2 Finding Homologs ......................................................................................... 13417.2.3 Selecting Regions to Mutate ......................................................................... 13517.2.4 Setting Up Residue Selection Criteria .......................................................... 135

Contents

Schrdingeviii

17.2.5 Selecting the Residues and Their Mutations ................................................ 13617.2.6 Setting Refinement Options for Mutated Residues....................................... 13717.2.7 Selecting Properties to Calculate.................................................................. 13817.2.8 Running the Mutation Job ............................................................................. 138

17

17

Referenc

Getting Hr Software Release 2014-3

17.2.9 Analyzing the Results ................................................................................... 13817.2.10 Summary .................................................................................................... 140

.3 Humanizing Antibodies by CDR Grafting ....................................................... 141

.4 Antibody Databases............................................................................................ 144

es .............................................................................................................................. 147

elp ........................................................................................................................... 149

Document Conventions

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Sans serif uppercaseBioLuminate 1.6 User Manual ixto the use of italics for names of documents, the font conventions that are used innt are summarized in the table below.

er locations in the current document or to other PDF documents are colored likeent Conventions.

ons of command syntax, the following UNIX conventions are used: braces { }hoice of required items, square brackets [ ] enclose optional items, and the bareparates items in a list from which one item must be chosen. Lines of commandwrap should be interpreted as a single command.

path, and environment variable syntax is generally given with the UNIX conven-tain the Windows conventions, replace the forward slash / with the backslash \ in

ctory names, and replace the $ at the beginning of an environment variable with a % For example, $SCHRODINGER/maestro becomes %SCHRODINGER%\maestro.

ferences are given in the Windows convention by default, with Mac equivalents in, for example CTRL+H (H). Where Mac equivalents are not given, COMMANDad in place of CTRL. The convention CTRL-H is not used.

ment, to type text means to type the required text in the specified location, and toeans to type the required text, then press the ENTER key.

to literature sources are given in square brackets, like this: [10].

Example Use

Project Table Names of GUI features, such as panels, menus, menu items, buttons, and labels

$SCHRODINGER/maestro File names, directory names, commands, envi-ronment variables, command input and output

filename Text that the user must replace with a valueCTRL+H Keyboard keys

Schrdingex r Software Release 2014-3

Chapter 1


Chapter 1: Introduction

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Proteitions aBioLuminate 1.6 User Manual 1verview of BioLuminate Featureste offers a wide range of tools for protein modeling, protein engineering, proteinptide analysis, and antibody modeling. In addition to the unique tools, BioLumi-es access to many of the related tools in the Schrdinger software suite. The BioLu-rface is a customization (profile) of the Maestro interface, designed for protein

l documents the unique tools and capabilities of BioLuminate, and provides refer-er documents for the related tools. A brief description of the tool set is given below,o the relevant parts of this manual or of other manuals. The descriptions are classi-ction. These tools are divided between the Tools menu, where the action does notime and may be interactive, and the Tasks menu, where a job may need to be runlarger amount of time.

rotein Analysis Tools analysis tools provide information on a protein and its properties. No change is protein structure.

n Structure Quality Viewer (Tools Protein Structure Quality): Show reports onions of protein parameters from standard values, in graphical and tabular form. Seeer 3.

e Analysis (Tasks Residue Analysis): Calculate energetic and other propertiesdues. See Chapter 4.

nsus Visualization (Tools Protein Consensus Viewer): Locate consensus waters,r ions and ligands in a set of homologs to a reference protein. See Chapter 5.

ive Protein Residues (Tools Reactive Residue Identification): Identify residuese prone to specified reactions, by matching sequence patterns and some structuralation. See Chapter 6.

gation Surface (Tasks Aggregation Surface): Predict regions on a protein surfaceve a propensity for aggregation. See Chapter 7.

n Interaction Analysis (Tasks Protein Interaction Analysis): Analyze the interac-t the interface of two proteins. See Chapter 8.


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Low Mode Vibrational Sampling (Tasks Low Normal Mode Analysis): Locate and visu-alize large-scale vibrational motions in a protein. See Chapter 9.

SiteMap (Tools Binding Site Identification): Locate druggable sites on a protein. See theSiteMap User Manual.

1.1.2 P

The proteinmissing infproteins by peptides.

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rotein Structure Tools structure tools allow you to fix structures from the PDB or other sources that areormation needed for modeling or are missing atoms, predict the structure ofhomology modeling, and predict the structure and stability of alpha helices in small

n Preparation Wizard (Tools Protein Preparation): Prepare proteins for modelingigning bonds, fixing structural defects, removing unwanted parts, assigning proton-nd tautomeric states, and refining the structure. See the Protein Preparation Guide.

Homology Modeling (Tasks Simple Homology Modeling): Predict the structureteins using homology modeling, where the homology is high and the alignment ofery and the template is straightforward. See Chapter 12.

ure Prediction (Tasks Advanced Homology Modeling): Predict the structure of-chain or multi-chain proteins, including multimers, by homology modeling. Seeer 3 through Chapter 5 of the Prime User Manual.

ment (Tasks Loop + Sidechain Prediction or )Tasks Implict Solvent Refine-+ Analysis): Refine protein structures by performing predictions of selected side or loops, or minimizations of various parts of protein structures. See Chapter 6 ofime User Manual.

eptide Toolse tools allow you to predict various properties of small peptides from theirsee Chapter 10.

e Helicity (Tasks Peptide Alpha Helicity): Predict the stability of alpha helices forpeptide sequences, using molecular dynamics.

e Docking (Tasks Peptide Docking): Dock peptides to a receptor, starting fromquence. The receptor is largely rigid, the conformational space of the peptide ised.

e QSAR (Tasks Peptide QSAR): Predict properties of small peptides using a (sequence-property) model based on peptide descriptors.


1.1.4 Protein Alignment and Docking ToolsThe alignment tools include tools that structurally superimpose two proteins (or structures),and a tool for docking one protein to another. These tools perform rigid-body translation of thestructures to

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obtain the best alignment.

inding Sites (Tools Binding Site Alignment): Align the sites on a set of proteinsch drug-like molecules can bind. See Chapter 7 of the Prime User Manual.

n Structure Alignment (Tools Protein Structure Alignment): Structurally align twore proteins, using secondary structure information as well as coordinates. Seeer 7 of the Prime User Manual.

position (Tools Superposition): Align two or more structures by minimizing the of a selected set of atoms. See Section 10.3 of the Maestro User Manual.

n-Protein Docking (Tasks Protein-Protein Docking): Predict how two proteinst, using a rigid body search algorithm. See Chapter 11.

rotein Mutation and Modification Tools

e Scanning (Tasks Residue Scanning): Systematically perform single muta-f protein residues to determine how energetic and other properties change, and toy mutations that can effect desired changes. See Chapter 15.

Maturation (Tasks Affinity Maturation): Perform multiple sequential mutationstein residues to optimize the binding affinity of two proteins or the stability of a. See Chapter 15.

ne Mutation (Tasks Cysteine Mutation): Locate residue pairs that can reasonablyisulfide bonds if one or both of the residues are mutated to cysteine and performtation, or locate disulfide bonds and mutate one of the residues to another type to

the disulfide bond. See Chapter 16.

e and Loop Mutation (Tasks Residue and Loop Mutation): Mutate a single resi- a standard or custom residue, invert the chirality of a residue, delete or insert mul-esidues in a single loop, or swap a loop for another loop. See Chapter 13.

link Proteins (Tasks Crosslink Proteins): Join two protein chains from their ter-ith a series of linkers, to produce a set of structures. See Chapter 14.


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1.1.6 Antibody ToolsBioLuminate provides a specialized set of tools for modeling antibodies, including managingdatabases of antibody structures, homology modeling of antibodies, antibody humanization,and antigen

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-antibody docking.

dy Prediction (Tasks Antibody Modeling Prediction): Predict the structure ofR region of an antibody by homology modeling, using homology and database

ds. See Section 17.1 on page 121.

dy Humanization: Residue Mutation (Tasks Antibody Modeling Humanizationsidue Mutation): Humanize an antibody by performing mutation of residuesd manually or on the basis of homology to human antibodies. See Section 17.2 on33.

dy Humanization: CDR Grafting (Tasks Antibody Modeling Humanization rafting): Humanize an antibody by grafting the CDR loops on to a human anti-

See Section 17.3 on page 141.

dy Database Management (Tasks Antibody Modeling Database Manage- Select, create, and update antibody databases. See Section 17.4 on page 144.

n-Protein Docking (Tasks Protein-Protein Docking): Dock an antigen to an anti-See Section 11.5 on page 75.

unning Schrdinger Softwarer applications can be run from a graphical interface or from the command line. Theites input and output files to a directory (folder) which is termed the working direc- run applications from the command line, the directory from which you run theis the working directory for the job. The BioLuminate interface is a customizationtro interface. You can also use the standard Maestro as your working interface.

Schrdinger program on a Linux platform, or start a Schrdinger job on a remote Linux platform, you must first set the SCHRODINGER environment variable to thedirectory for your Schrdinger software. To set this variable, enter the followingt a shell prompt:

setenv SCHRODINGER installation-directory export SCHRODINGER=installation-directory


Once you have set the SCHRODINGER environment variable, you can run programs and utilitieswith the following commands:

$SCHRODINGER/program &$SCHRODINGER/utilities/utility &You can sta

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rt the BioLuminate interface with the following command:

GER/maestro -profile BioLuminate &

a good idea to change to the desired working directory before starting the BioLu-face. This directory then becomes the working directory.

way of running Schrdinger applications on a Windows platform is from a graph-e. To start the BioLuminate interface, double-click on the BioLuminate icon, on aject, or on a structure file; or choose Start All Programs Schrodinger-2014-3ate. You do not need to make any settings before starting BioLuminate or runninghe default working directory is the Schrodinger folder in your Documents folder.

to run applications from the command line, you can do so in one of the shells thatd with the installation and have the Schrdinger environment set up:

dinger Command PromptDOS shell. dinger Power ShellWindows Power Shell (if available). en these shells from Start All Programs Schrodinger-2014-3. You do not needhe path to a program or utility when you type the command to run it. If you wantnix-style utilities (such as awk, grep, and sed), preface the commands with sh, orither of these shells to start a Unix-style shell.

y way of running Schrdinger software on a Mac is from a graphical interface. ToLuminate interface, click its icon on the dock. If there is no BioLuminate icon onu can put one there by dragging it from the SchrodingerSuite2014-3 folder in your folder. This folder contains icons for all the available interfaces. The defaultectory is the Schrodinger folder in your Documents folder ($HOME/Documents/er).ftware from the command line is similar to Linuxopen a terminal window andram. You can also start BioLuminate from the command line in the same way as ondefault working directory is then the directory from which you start BioLuminate.


Schrdinge6

You do not need to set the SCHRODINGER environment variable, as this is set in your defaultenvironment on installation. To set other variables, on OS X 10.7 use the command

defaults write ~/.MacOSX/environment variable "value"

and on OS X

launchctl

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tarting Jobs from the BioLuminate Interfaceb from the BioLuminate interface, you open a panel from one of the menus (e.g.e settings, and then submit the job to a host or a queueing system for execution.ettings are described in the help topics and in the user manuals. When you haveking settings, you can use the Job toolbar to start the job.

rt a job immediately by clicking Run. The job is run on the currently selected hostrent job settings and the job name in the Job name text box. If you want to changee, you can edit it in the text box before starting the job. Details of the job settings in the status bar, which is below the Job toolbar.

to change the job settings, such as the host on which to run the job and the numberrs to use, click the Settings button. (You can also click and hold, and choose Jobm the menu that is displayed.)

en make the settings in the Job Settings dialog box, and choose to just save theclicking OK, or save the settings and start the job by clicking Run. These settingsto jobs that are started from the current panel. to save the input files for the job but not run it, click the Settings button and chooselog box opens in which you can provide the job name, which is used to name the

les are written to the current working directory.

s button also allows you to change the panel settings. You can choose Read, to readm an input file for the job and apply them to the panel, or you can choose Resetet all the panel settings to their default values.

o set preferences for all jobs and how the interface interacts with the job at various is done in the Preferences panel, which you can open at the Jobs section byeferences from the Settings button menu.


Note: The items present on the Settings menu can vary with the application. The descriptionsabove cover all of the items. Jaguar has an Edit item and extra functions for the Readand Write items, which are described later in the manual.

The icon on the Job Status button shows the status of jobs for the application that belong to thecurrent projwhen the lafully.

Clicking thactive jobs the bottom.launched, rurow to openMonitor panopen. If a jstatus. Click Jobs are runferring filesoperates, as

1.4 CThe use of t

BioLumina

BioLuminate 1.6 User Manual 7

ect. It starts spinning when the first job is successfully launched, and stops spinningst job finishes. It changes to an exclamation point if a job is not launched success-

e button shows a small job status window that lists the job name and status for allsubmitted for the application from the current project, and a summary message at The rows are colored according to the status: yellow for submitted, green fornning, or finished, red for incorporated, died, or killed. You can double-click on a the Monitor panel and monitor the job, or click the Monitor button to open the

el and close the job status window. The job status is updated while the window isob finishes while the window is open, the job remains displayed but with the new anywhere outside the window to close it.

under the Job Control facility, which manages the details of starting the job, trans-, checking on status, and so on. For more information about this facility and how it well as details of the Job Settings dialog box, see the Job Control Guide.

iting BioLuminate in Publicationshis product should be acknowledged in publications as:

te, version 1.6, Schrdinger, LLC, New York, NY, 2014.

Schrdinge8 r Software Release 2014-3

Chapter 2


Chapter 2: The BioLuminate Interface

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Many encesBioLuminate 1.6 User Manual 9minate interface is a customized form of the Maestro interface that is speciallyr biologics use. It inherits most of the capabilities of the Maestro interface (thoughifferently), and it has features of its own. r focuses on the features that are unique to BioLuminate. Summaries of the maintures are given, with references to the Maestro User Manual for details. If you have

aestro, you should be able to gain a basic understanding of its operation from this

r to use the standard Maestro interface, you can do so. Most of the capabilities ofte are available from the BioLuminate submenu of the Applications menu, and some on the Tools menu.

en the BioLuminate interface as follows:

ows: Double-click the BioLuminate icon on the desktopGo to Applications SchrodingerSuite2014 and double-click the BioLuminate icon: Start Maestro and choose BioLuminate in the Choose Profile dialog box, or usemmand $SCHRODINGER/maestro -profile BioLuminate

e Main Windowinate main window opens with the following features displayed by default:

bar. This is at the top of the window on Linux and Windows, and is the menu bar Mac.

ger toolbar. This toolbar is just below the menu bar on Linux and Windows, and at of the window on the Mac. Each label on this toolbar displays or hides another

r. By default they are all hidden, as much of their function is available in the Toggle See Section 2.4 of the Maestro User Manual for details of the toolbars.

e Table. This dockable panel is displayed on the right side of the main window. Youdock it from the main window and redock it with the docking button.

other panels are also dockable. You can change the docking behavior in the Prefer- panel (Edit Settings Preferences, or CTRL+,)


Schrdinge10

Workspace. This is the large black area that occupies the main part of the main window.It is where structures are displayed, along with any associated objects such as surfacesand text labels.

Status bar. This bar is below the Workspace. At the left is a button that displays informa-tion oninformtus baatom, see Se

Menu bar

Workspar Software Release 2014-3

what jobs are running, which you can click to open the Monitor panel for detailedation on your jobs. When the pointer is not over an atom in the Workspace, the sta-

r gives information on the contents of the Workspace. When the pointer is over anthe status bar gives information on the identity of the atom. For more information,ction 2.5 of the Maestro User Manual.

Figure 2.1. The BioLuminate main window.

Manager toolbar Toggle table

ce Status bar Auto-help


Auto-help. This orange-yellow bar at the bottom of the main window gives tips on thecurrent action that can be performed in the Workspace.

There are several other components of the main window that can be displayed when needed, bychoosing Edit Settings and then choosing the component. These components include theSequence Vtoolbar (alsthe Workspview of thedisplay.

2.2 SWhen you stures that MEach such multiple mstructure (cof the strucwith the struties of indiv

To add structhe Protein tures. To gchoose FileSection 3.1

To see a list(T) or Winproperties, managemendetails of thManual. Thlittle differeface is splitBioLuminate 1.6 User Manual 11

iewer, which displays the sequences of proteins that are in the Workspace; the Findo opened with CTRL+F, F), which you can use to find structural components inace, like chains or residues; and the Clipping Planes window, which shows a top Workspace and the planes where the structures in the Workspace are clipped for

tructures and Projectstart BioLuminate, a new, temporary project is created. Projects are the data struc-aestro uses to store and manage molecular structures, such as proteins and ligands.molecular structure in a project is stored in an entry. An entry can consist ofoleculeschains of a protein, waters, cofactors, ions, and so on. The molecularoordinates, charges, and bonding information) is stored along with any propertiestures, such as the PDB ID and crystallographic information, surfaces associatedcture, and display information for showing the structure in the Workspace. Proper-idual atoms are stored as well as properties of the structure as a whole.

tures to the project, you can import them from an external source, such as a file orData Bank (PDB). To import structures from a file, choose File Import Struc-

et structures directly from the PDB (either from a local copy or from the web), Get PDB. Details of both of these methods for importing can be found inof the Maestro User Manual.

of all the entries in the project, you can open the Project Table panel with CTRL+Tdow Show Project Table. This panel lists the entries in the project with their

and provides ways of doing actions on the entries and their properties, such ast tasks, sorting, grouping, plotting, import and export of entries and properties. Fulle operation of the Project Table can be found in Chapter 9 of the Maestro Usere menu organization in the Project Table panel in the BioLuminate interface is ant from that in the standard Maestro interface: the Table menu in the standard inter- between the Table menu and the Tools menu in the BioLuminate interface.


Schrdinge12

2.3 The Toggle TableThe Toggle Table panel can be used to interact with structures in the Workspace. The panel hasa set of buttons at the top for quick access to some common actions. The main part of the panelconsists of be used to pmake selectand rows foBelow the r

When the toWorkspace,toggles.

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a row for each entry in the Workspace, with a set of buttons, or toggles, that canerform actions. These buttons are actually cascading menus, from which you can

ions. In addition to the rows for each entry, there is a row for all entries, labeled All,r selected atoms in the Workspace. The entry rows are labeled with the entry title.ows is a button for including entries in the Workspace.

ggle table is displayed, a set of shortcut (or context) menus is also available in the which you open by right-clicking. These menus offer the same functions as the

tion with the Workspace provided by the Toggle Table panel is very similar to thef PyMOL. If you are familiar with PyMOL, this interface should be easy to learn. Ifiliar with Maestro but not with PyMOL, you can close the Toggle Table panel anddard Maestro interaction with the Workspace.

s of the Toggle Table panel are described in detail in the following subsections.

terminology used in the Toggle Table panel is the PyMOL terminology, which isewhat different from that used in standard Maestro.

uick Access Buttons

buttons at the top of the Toggle Table panelick access to a number of actions, some of

lso on the menus.

Reset the view to the default view, in which the view axes are aligned with thenate axes of the structure.

Change the view of the Workspace so that all atoms fit inside the Workspace

Orient the Workspace structures by translating and rotating them so that the cen-mass is at the origin, the largest principal axis lies on the x axis, and the second-t principal axis lies on the y axis.

This operation changes the coordinates of the structures, not just the coordinatesof the view.


DrawSave an image of the Workspace to a file in TIFF, JPEG, or PNG format. (Same asFile Save Image.)

HelpOpen the help topic for the panel in your browser.

RayPyMOvariab

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Selectspace.BioLuminate 1.6 User Manual 13

Use PyMOL to draw a ray-traced image of the Workspace. This feature requiresL to be installed, and either the PYMOL4MAESTRO or PYMOL_PATH environmentle must point to the directory where the PyMOL executable file resides.

ctClear the current Workspace selection.

Rotate the Workspace back and forth smoothly. Click once to start rotation, clickto stop.

reenSwitch Maestro to full screen mode. To exit full screen mode, press thePE key or click this button again.

able Rows

n the Toggle Table has a title and a set of fivens, labeled A, S, H, L, and C. These buttonsing menus, and are described in the following

ree distinct types of rows in the Toggle Table:

ll row: Actions taken in this row apply to all entries in the Toggle Table.

rows: These rows apply to a single project entry that is currently in the Workspace.ame of the row is the Title property of the entry. Entry rows are deleted when thes excluded from the Workspace, and a new row is added when an entry is added torkspace.

ion rows: When a group of atoms is selected, a selection row is added to the table.s in this row apply to the group of atoms that was selected to create this row andpply after those atoms are no longer selected. The selection row named (Selection)s refers to the most recent group of selected atoms. If a new selection is made whiletion row is active, that row now refers to the new set of selected atoms. Only oneon can be active at a time.

ion rows can be renamed: renamed selection rows always refer to the same set of regardless of subsequent Workspace selections. To rename a selection row, chooseename Selection. Selection row names are always enclosed in parentheses.

ion rows are deleted when any atoms they refer to are removed from the Work- To delete a selection row, choose A Delete Selection.


Schrdinge14

Using the A button submenus, selection rows can also be duplicated, copied, andextracted to define a new entity that is independent of the objects from which the selec-tion was originally derived.

Some operations or menu items change based on whether they are being applied to the All row,an entry rowentry rows.after the des

Clicking thWorkspace.showing orspace, so anwell as the

For instancClean fromable amounstructures fr

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The A buttostructure de

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, or a selection row. The descriptions below primarily describe the behavior for When a behavior changes for the All row or a selection row, the change is notedcription.

e name of the All row or an entry row changes the visibility of that object in the When the object's visibility is off, the name is dimmed. This is a quick way of hiding the atoms in entries. Hiding atoms does not remove them from the Work-y action taken on the entry or the entire Workspace applies to the hidden atoms as

visible atoms.

e, if the Workspace contains ten entries and only one entry is visible, choosing the A menu in the All row operates on all ten structures. This may take a consider-t of time to complete and lead to unexpected results. Similarly, if a panel importsom the Workspace, it imports all ten structures rather than just the visible structure.

e name of the current selection row deselects the selected atoms, but the selectionined. Clicking the name of any other selection row selects the atom group that theo, and any currently selected atoms that are not part of this atom group are dese-

he Action Menu

n opens the Action menu, from which you can choose a variety of actions for thefined by the table row. Not all of the actions are available in every table row.

Changing the Viewur actions on the Action menu change the view (camera angle) of the structurehe table row. The Workspace coordinate system has the origin in the middle of the the x axis is the horizontal axis, the y axis is the vertical axis, and the z axis is of the screen.

Change the view of the Workspace so that all the atoms in the structure fit insidel the Workspace area. In the All row, this action is equivalent to clicking the Zoom at the top of the panel.

Orient the structure by translating and rotating it so that the center of mass is atigin, the largest principal axis lies on the x axis, and the second-largest principales on the y axis. When you apply this operation to the selection, it is the center of


mass and principal axes of the selection that are used, but the entire structure is reori-ented.

Note: This operation changes the coordinates of the structures, not just the coordinatesof the view (the camera angle).

Centecentro

OriginThe ce

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Ligandligandbons ccontacBioLuminate 1.6 User Manual 15

rCenter the structure in the Workspace, by translating the structure so that itsid is at the center of the Workspace.

Set the center around which rotation is performed to the centroid of the structure.ntroid need not be at the Workspace origin.

Minimizing the Structure Energynimize the energy of the Workspace or the selected atoms using the OPLS_2005by choosing Clean from the Action menu. The current selection is updated (or an created) to refer to the minimized atoms. To avoid starting a lengthy calculationr performed in the background, Clean is limited to structures of fewer than 1000

Changing the Appearance of Structuresctions on the Preset submenu change the appearance (representation) of the struc-various preset styles. Some of these representations take a little time to set up, and ar is displayed at the bottom of the table.

Show proteins as ribbons (C alpha trace) colored by chain, ligands and boundor as sticks, and solvent, disulfides and ions as lines. Atom colors are not changed.

(no solvent)Same as Simple, but no waters are shown.d StickShow atoms and bonds in ball and stick, with no protein ribbons.

torShow the protein as tubes with residues colored by the B-factors of the resi-in a relative scheme that ranges from shades of blue, through green and yellow to

icalShow atoms as sticks, colored with rainbow colors by residue position, andolar contacts (hydrogen bonds) as yellow dotted lines.Show proteins as ribbons colored with rainbow colors by residue position, ands as lines. All protein atoms within 5 of the ligand are shown as lines, with car-olored with rainbow colors by residue position. Waters are shown as sticks, polarts are shown as yellow dotted lines, and the view is zoomed in to the atoms shown.


Schrdinge16

Ligand SitesThis submenu shows variations on the Ligand preset that alter the way theprotein or region around the ligand is shown:

CartoonShow proteins as cartoons rather than ribbons. S

o

Ta

a

Ds

Mm

s

Prettyligand

Pretty

Public

Publicsided.

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2.3.3.4

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olid surfaceShow the molecular surface of the protein around the ligand as anpaque surface, colored by the nearest non-hydrogen atom.ransparent surfaceShow the molecular surface of the protein around the ligands a semi-transparent surface, colored by the nearest non-hydrogen atom; showtoms and bonds as sticks. ot surfaceShow the molecular surface of the protein around the ligand as a dot

urface, colored by the nearest non-hydrogen atom; show atoms and bonds as sticks. esh surfaceShow the molecular surface of the protein around the ligand as aesh surface, colored by the nearest non-hydrogen atom; show atoms and bonds as

ticks.

Show proteins as cartoons colored with rainbow colors by residue position ands as sticks.

(with solvent)Same as Pretty but waters are shown as ball and stick.ationSame as Pretty, but protein helices are two-sided.

ation (with solvent)Same as Pretty (with solvent), but protein helices are two-

n InterfaceColor ribbons and carbons by chain, show anything not at a proteince as cartoon ribbons, and interface residues as ball and stick. Non-carbon atomstheir previous coloring. Interface residues are residues in a chain with more thanoms that are within 4.5 of another chain with more than 300 atoms.dyShow everything as cartoon ribbons colored by antibody structure. The lightis colored in red hues, the heavy chain is colored in blue hues, and everything elsered green. Constant regions are dark hues and the CDR regions are bright hues.

ght chain L1-L3 loops are shaded orange to brown, while the heavy chain H1-H3aded grey-blue to cyan.

ltShow everything as lines with default colors (colored by element with greens).

Displaying Polar Contacts n on or off the display of polar contacts (hydrogen bonds) between various groupsm the Polar Contacts submenu. The display is turned on with A Polar Contacts

s turned off with A Polar Contacts Remove All. The atom groupings are:


Within Object Involving Side Chains Involving Solvent Excluding Solvent Exclud Exclud Just In Just In To Oth To Oth To Any To Any

Each menu

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ing Main Chain ing Intra-Main Chain tra-Side Chain tra-Main Chain er Atoms In Entry er Atoms In Entry Excluding Solvent Atoms Atoms Excluding Solvent

choice clears any previous choice before applying the new choice.

t more flexibility in choosing the atom groups between which polar contacts are can use the Non-Bonded Interactions panel. Choose Style H-Bonds and Halogen the menu bar at the top of the Workspace to open this panel. You can also use thelbar button on the Measurements toolbar.

Generating an Atom Selectionect atoms in predefined groups by choosing A Generate Selection and thene group. The Generate item is not available for the All or Selection rows. Theroups are:

ll atoms.

erBackbone and side-chain atoms.

icLigand atoms.

tWater atoms.

e ResiduesAll residues with solvent-exposed surface area greater than 10 2.n InterfaceResidues in a chain of more than 300 atoms that are within 4.5 ofr chain of more than 300 atoms.

tions can also be generated by picking atom groups in the Workspace. To set them group you want to pick, choose Edit Pick Mode then the atom group namesidues, Chains, Molecules, or Entries), using the menu bar at the top of the Work-can also set the mode by typing the first letter of the name when the pointer is in the To pick an atom group, click on an atom in the Workspace that belongs to the can see information about the atom in the Status bar when you pause the pointerm.


Schrdinge18

2.3.3.6 Displaying Atoms Related By Crystallographic SymmetryIf you want to see atoms from nearest-neighbor crystal symmetry mates of your structure, youcan choose A Generate Symmetry Mates. To show symmetry-related atoms requirescrystal symmetry information to be present for the structure. You should also ensure that youhave only tapplies to th

The Symmewhich symmplaced fromsymmetry mthe toggle tMates S

2.3.3.7

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he structure that you want to see the related information for, because this actione entire Workspace.

try Mates submenu items control the cutoff distance from the original structure foretry mate atoms should be displayed. Note that no matter how far the cutoff is

the original structure, only the nearest-neighbor mates are created and shown. Theates are created as separate, temporary entries (scratch entries) and are shown inable. You can remove the symmetry mates by choosing Generate Symmetryhow None.

Modifying an Atom Selection item is available for selection rows only, and replaces Generate on the Actionlows you to alter the group of selected atoms to include or exclude other atoms.ify action, the selection row applies to the new group of atoms.

actions all have a choice of atom groups to which they apply.

dselect all atoms or residues within a given distance from the current set of, and deselect the current set of atoms. The distance is chosen from the submenu,n encompass atoms only or be filled to entire residues that have any atoms withinosen distance.

dExpand the current selection to include all atoms or residues within a given dis-from the current set of atoms. The distance is chosen from the submenu, and canpass atoms only or be filled to entire residues that have any atoms within the cho-

stance.

Expand the current selection to include all atoms or residues within a givenr of bonds from the current set of atoms.

Deselect the current set of atoms and select all other atoms within a given atom The atom groups can be chosen from the submenu:

ithin ObjectsAll atoms in the entry that are not part of the selection are selected.ithin ChainsIn each chain that contains selected atoms, the unselected atoms are

elected, and the selected atoms are deselected.ithin ResiduesIn each residue that contains selected atoms, the unselected

toms are selected, and the selected atoms are deselected.


Within MoleculesIn each molecule that contains selected atoms, the unselectedatoms are selected, and the selected atoms are deselected.

Within AnyAll atoms in the entire Workspace that are not part of the selection areselected.

Compgroups

R C O M C

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O S V P O S IBioLuminate 1.6 User Manual 19

leteAdd all other atoms within a given atom group to the selection. The atom can be chosen from the submenu.

esiduesIn each residue that contains selected atoms, all atoms are selected.hainsIn each chain that contains selected atoms, all atoms are selected.bjectsIn each entry that contains selected atoms, all atoms are selected.oleculesIn each molecule that contains selected atoms, all atoms are selected.-alphasAll alpha carbons for residues within the selection are selected. All othertoms are deselected.

ct toReduce the selection to only those atoms within a specific group that are cur-selected. The available atom groups are:

bjectRestrict the selection to atoms in a specific entry, chosen from the sub-enu.

electionRestrict the selection to atoms in a specific selection row, chosen fromhe submenu.isibleRestrict the selection to atoms that are visible.olymerRestrict the selection to backbone and side-chain atoms.rganicRestrict the selection to ligand atoms.olventRestrict the selection to water atoms.

norganicRestrict the selection to atoms other than H, C, N, O, F, P, S, Cl, Br, or I.

eInclude additional atom groups in the current selection. The available atom are:

bjectInclude atoms in a specific entry, chosen from the submenu.electionInclude atoms in a specific selection row, chosen from the submenu.isibleInclude all visible Workspace atoms.

eExclude specific atoms from the selection. The available atom groups are:

bjectExclude atoms in a specific entry, chosen from the submenu.electionExclude atoms in a specific selection row, chosen from the submenu.isibleExclude atoms that are visible.olymerExclude backbone and side-chain atoms.rganicExclude ligand atoms.olventExclude water atoms.

norganicExclude atoms with element other than H, C, N, O, F, P, S, Cl, Br, or I.


Schrdinge20

2.3.3.8 Removing SelectionsFor the All row, Delete Selections removes any selection rows from the Toggle Table. All atomsare deselected but are otherwise unaltered.

For selectiothis selectio

2.3.3.9

You can chwith the Rename in the

You can chfor the defacan also ren

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2.3.3.10

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For selectioentry is creation.

2.3.3.11

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To clear the

2.3.3.12

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n rows Delete Selection just removes the row from the Toggle Table. The atoms inn group are deselected but otherwise remain unaltered.

Renaming Rowsange the name of an entry row, and thereby change the Title of the project entryname action. A text box is displayed instead of the name, and you can type a new box. If you decide you do not want to change the name after all, press ESC.

ange the name of a selection row with the Rename Selection action. If you do thisult selection row, the selection is preserved for future use as a named selection. Youame named selection.

and not available for the All row.

Duplicating Rowsplicate table rows with the Duplicate action, with the exception of the All row. Theferent for entry rows and for selection rows.

ws, the action creates a new project entry below the entry that is the duplicate of thestructures remain in the Workspace and are listed in the Toggle Table.

n rows, this action creates a duplicate selection row in the Toggle Table. No projectted. This can be useful if you want to use a selection as the basis for another selec-

Removing Entries from the Workspace(exclude) an entry from the Workspace, choose A Remove from Workspace foremoving an entry from the Workspace just means that it is no longer in youra. The entry remains in the project, and is listed in the Project Table. You can add itWorkspace by using the Include in Workspace button or the Project Table. Workspace entirely, choose Remove Everything from Workspace in the All row.

Deleting Entries from the Projectn entry from the project, choose Delete from Project in the entry row. The structure

from the Workspace and from the project. It no longer appear in the Project Table.


2.3.3.13 Creating Project EntriesYou can create new project entries either from a selection or from an entry row, by choosingCopy to New Project Entry. The new project entry is created by copying the selected atoms orentries, and it is added to the Workspace. This command is the same as Duplicate if you chooseit for an ent

To create a you can chothe atoms in

2.3.3.14

You can addgens Reremoved froselection ar

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2.3.3.16

To computeaction. The

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The computext. They aBioLuminate 1.6 User Manual 21

ry row.

project entry by removing atoms from entries and placing them into a new entry,ose Extract to New Project Entry in a selection row. The new project entry contains the selection, and the atoms are deleted from their current structure.

Adding and Removing Hydrogens or remove hydrogen atoms from a row by choosing Hydrogens Add or Hydro-move. If you perform this action in the All row or an entry row, the atoms arem the structure. If you perform this action in a selection row, the hydrogens in the

e removed, or they are added to complete the valences of the atoms in the selection.

o add hydrogens from the main menu bar with Edit Add Hydrogens or from the.

Removing Watersove waters from structures with the Remove Waters action. If you perform this

e All row or an entry row, the atoms are removed from the structure. If you performn a selection row, the waters in the selection are removed from the structure.

Computing Properties simple properties of the object (selection or entry), you can use the Computeproperties you can compute are:

CountThe number of atoms.

l Charge SumSum of atom formal charges.

l Charge SumSum of atom partial charges.

e AreasCompute surface areas. Solvent-Accessible surface area (SASA) uses at radius of 1.4 while Molecular surface area uses the same algorithm but with not to expand the atomic radii. The surface area is computed for the object in the con- the visible atoms in the Workspace.

ted properties are displayed in a window that opens, and you can copy and paste there not stored in the Project Table.


Schrdinge22

2.3.4 The Show MenuThe S button opens the Show menu, which contains commands that alter the display of struc-tures in the Workspace. There are three different types of display for structures:

Atomi Ribbo Surfac

Each atom representatiwith lines, cously by botations. If aexisting repshown withStick menu and stick re

The commo

Lines

Sticks

Ball an

Ribbo

Cartoo

Label

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These itemsfrom the Shsubmenu, thr Software Release 2014-3

c representations such as lines, sticks, ball and sticks or spheresn representations such as ribbons and cartoonse representations such as solid or mesh surfaces

may have one of each representation type active at once, but cannot have multipleons of the same type active. For instance, an atom can be shown simultaneouslyartoon ribbons and a mesh surface. However, an atom cannot be shown simultane-th ball and stick and sphere representations because they are both atomic represen-n action is chosen to show an atom with a representation in the same category as anresentation for that atom, the existing representation is removed and the atom is the new representation. For instance, if an atom is shown as lines, and the Ball anditem is chosen, the lines representation is removed and the atom is shown with ballpresentation.

n representations that can be applied are:

Set the atomic representation to lines (wire frame).Set the atomic representation to sticks (tube).d StickSet the atomic representation to ball and stick.

nSet the ribbon representation to ribbon (CA trace tube).nSet the ribbon representation to cartoons.

Show any labels defined for this structure.

ndedSet the atomic representation of any atom with no attachments (bonds) to(wire frame). These atoms appear as small stars. No change is made to atoms thatttachments (bonds). esSet the atomic representation to spheres (CPK). The sphere radii are the vanaals radii of the atoms.

nded SpheresSet the atomic representation of any atom with no attachments) to spheres (CPK). No change is made to atoms that have attachments (bonds). appear on both the Show menu itself and on the As submenu. When you chooseow menu, the representation is added to the display. When you choose from the Ase previous representation is replaced by the new choice.


For instance, a residue shown with lines and cartoon ribbons is shown as only ball and stick ifS As Ball and Stick is chosen, but is shown as cartoon and ball and stick if S Ball andStick is chosen.

Two commands on the menu for entry rows and the All row create and display molecularsurfaces. Ththe surface

Mesh Surfac

The remainsticks or sph

Organ Main C Side C Disulfi

2.3.5 T

The H buttospace. To rfeature for representati

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Atoms

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Label

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Water

HydroBioLuminate 1.6 User Manual 23

e surface is created if it does not exist, otherwise the color and representation ofis changed.

Display a mesh molecular surface colored by current atom color.eDisplay a solid molecular surface colored by current atom color.

ing four items have submenus from which you can set the representation to lines,eres:

icSet the atomic representation of backbone and side-chain atoms.hainSet the atomic representation of backbone atoms.hainSet the atomic representation of side-chain atoms.desSet the atomic representation of disulfide atoms.

he Hide Menu

n opens the Hide menu, which contains commands that hide features in the Work-edisplay these features, use the Show menu. Each item hides only the particularthe row, and leaves any other features as they are. Hiding atoms also hides anyon of the bonds to those atoms.

hingHide all features: atomic, ribbon, and surface representations and labels.

Hide atoms and bonds.

Hide all ribbon representations.

nHide all ribbon representations.

Hide labels. The labels remain defined and can be redisplayed.

nded AtomsHide atoms with no attachments, such as Cl ions.

Hide surfaces.

eHide surfaces.

hainHide backbone atoms.

hainHide side-chain atoms.

sHide water atoms.

gensHide nonpolar or all hydrogens, as chosen from the submenu.


Schrdinge24

Symmetry MatesRemoves all crystal symmetry mates from the Workspace. This is aWorkspace setting, so affects all symmetry mates in the Workspace.

Polar ContactsRemove polar contact (hydrogen bond) markers. All Oth

in the

2.3.6 T

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Labels can Label. If ththey need tagain.

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Atom Eleme Residu Residu Chain B-facto Occup VDW R

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ersHide everything for all atoms in the Workspace other than the atoms definedrow.

he Label Menu

n opens the Label menu, which contains commands that label features in the Work-ss otherwise specified, labels are created for every atom the row applies to. Atomed by these commands are not cumulative. Any existing atom labels are removednes are created.

be cleared from the Workspace with L Clear. They can be hidden with H ey are hidden, they can be redisplayed with S Label, while if they are cleared,o be created (usually by other Label menu commands) before they can be shown

Label the first carbon atom in each residue with the three-letter PDB code andber.

bel the first and last residue in each chain with the chain name.

et of commands offers a choice of the label content, including identifiers andperties.

NameLabel each atom with its PDB atom name.nt SymbolLabel each atom with its element symbol.e NameLabel each atom with the three letter PDB code of the residue it is in.e IdentifierLabel each atom with the residue number of the residue it is in.

IdentifierLabel each atom with the name of the chain it is part of.rLabel each atom with its PDB B-factor value, if it exists.

ancyLabel each atom with its partial occupancy data if it exists.adiusLabel each atom with its van der Waals radius.

PropertiesSubmenu with other properties that can be used for labels:

ormal ChargeLabel each atom with its formal charge.artial Charge (0.00)Label each atom with its partial charge to two decimallaces.artial Charge (0.0000)Label each atom with its partial charge to four decimallaces.acroModel Text TypeLabel each atom with its MacroModel atom type.


MacroModel Numeric TypeLabel each atom with the numerical index for the Mac-roModel atom type.

StereochemistryLabel each atom with E,Z and R,S stereochemistry.

Atom IdentifiersSubmenu of atom identifiers that can be used for labels.

2.3.7 T

The C buttotions by vaentry. The s

Color for C, color s

Rt

Ca

c

r

Ca

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m

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Color

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RpBioLuminate 1.6 User Manual 25

he Color Menun opens the Color menu, which contains commands to color the atom representa-rious coloring schemes including by element, chain, substructure, B-factor andchemes are grouped into classes, each of which is represented by a menu item.

by ElementColor H, C, N, O and S atoms. Default colors are white for H, greenblue for N, red for O and yellow for S. There are several choices for modifying thecheme on this submenu.

eset HNOSSet H, N, O and S atoms to their default color. Carbon atoms remainheir current color.ustom Color {C}HNOSPick the color for carbon atoms and set H, N, O, and Stoms to their default color. Clicking on the menu item opens a palette of colors tohoose from for carbon atoms, while selecting Recent Color Choices lists the mostecent colors chosen by this command.ustom Color {H}CNOSPick the color for hydrogen atoms and set C, N, O, and Stoms to their default color. Clicking on the menu item opens a palette of colors tohoose from for hydrogen atoms, while selecting Recent Color Choices lists theost recent colors chosen by this command.

by ChainColor atoms by chain:

y Chain (Carbons)Change the color of carbon atoms only.y Chain (Calpha)Change the color of alpha carbon atoms only.y ChainChange the color of all atoms.hainbowsEach chain is colored with rainbow colors.

by SubstructureHelices, sheets and loops are colored by the chosen colore. All other atoms retain their current color.

by SpectrumColor all residues by a spectrum of colors.

ainbow (Carbons)Color carbon atoms only with rainbow colors by residue posi-ion. The chain is divided into segments, each of which has residues of the sameolor. ainbow (Calpha)Color alpha carbon atoms only with rainbow colors by residueosition.


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RainbowColor all atoms with rainbow colors by residue position. B FactorsColor atoms by the residue B factor. B Factors (Calpha)Color alpha carbon atoms only by the residue B factor.

AutoColor groups of atoms via a cycle of colors:

C A C A

Custoing onColor

2.4 SThe Workspfor the selecWorkspace,for the selehold over athen right-c

Most of theSelection sshortcut meof the Wormenu also (displayed) Workspace.r Software Release 2014-3

arbonscolor carbon atoms by the next color in the cycle.ll Atomscolor all atoms by the next color in the cycle.arbons by Objectcolor carbon atoms a different color for each entry.ll Atoms by Objectcolor all atoms a different color for each entry.

m Color All AtomsChange the color of all atoms to a single custom color. Click- the menu item opens a palette of colors to choose from, while selecting RecentChoices lists the most recent colors chosen by this command.

hortcut Menusace has two shortcut (context) menus when the Toggle Table panel is open. One isted atoms, and one is for the entire Workspace. To show the shortcut menu for the right-click and hold in an empty part of the Workspace. To show the shortcut menuction, right-click and hold over one of the selected atoms. If you right-click andn unselected atom, the selection changes: its the same as picking that atom first,licking and holding on it.

menu items are the same as those on the Toggle Table buttons or button menus. Thehortcut menu has a Disable item, which turns off the selection. The Workspacenu has Enable and Disable actions, which you can use to display or undisplay anykspace rows. These actions are also available from some of the submenus. Thishas a Select action, which you can use to create a selection from the visibleatoms. It also allows you to operate on the visible atoms only or on all atoms in the

Chapter 3


Chapter 3: Analyzing Protein Quality

The qualityPDB. You cProtein StruQuality.

If there is acan display

At the top owith variouthey are alreporting, b

The remainPlot tab, and

3.1 RThe Ramacplotted as trplot has thscheme seleCyan/Red a

Pausing thehighlights tWorkspace displayed athe panel. C

The plot are

Below the pspace structdues and mthe WorkspAnalyze WoBioLuminate 1.6 User Manual 27 of a protein structure is often measured by deviations from values reported in thean analyze a protein and display tabular and graphical reports on its quality in thecture Quality Viewer panel, which you open by choosing Tools Protein Structure

protein in the Workspace, it is analyzed when you open the panel. Otherwise, you a protein in the Workspace and click Analyze Workspace to perform the analysis.

f the panel, the protein table lists the chains in the protein that is analyzed alongs measures of the overall structure quality. You can analyze multiple proteins andl listed in the table, and you can select multiple chains in a single protein forut you cannot select multiple proteins.

der of the panel consists of two tabs that show different data: the Ramachandran the Protein Report tab.

amachandran Plothandran Plot tab displays a Ramachandran plot of the dihedral angles. Glycines areiangles, prolines are plotted as squares, all other residues are plotted as circles. Theree regions: favored, allowed, and disallowed, which are colored by the colorcted from the option menu at the bottom of the tab. There are two schemes: Green/nd Red/Yellow/White, for coloring the favored, allowed and disallowed regions.

cursor over a point displays information for that residue at the top of the panel, andhe residue in the Workspace. Clicking on a point selects the point and zooms theimage in to that residue, and highlights it with pale yellow markers. The point iss an outline instead of solid black. The residue information is displayed at the top oflick again on the point to deselect it.

a has a toolbar, which is described in Section 3.3.

lot, you can select options to change the appearance of the residues in the Work-ure for each of the three regions. The appearance is changed by coloring the resi-odifying the molecular representation. The coloring is applied when you analyzeace or change the color scheme, so you should set these options first, and then clickrkspace or change the color scheme. Deselecting any of these options does not


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revert the crevert it.

3.2 PThe properSelecting tarows, highlselected pro

Figurer Software Release 2014-3

olor scheme to the original scheme, so you must change the scheme manually to

rotein Reportty table displays a list of values of the property chosen from the Display menu.ble rows zooms the Workspace view in to the structural features listed in those

ights them with a change in representation, and selects them. The average of theperty over the entire structure is displayed below the table.

3.1. The Protein Structure Quality Viewer panel, Ramachandran Plot tab.


The propertThe plot areand blue dawhich is givlighted portpoints in th

If you wancurrent probuttons ope

FiguBioLuminate 1.6 User Manual 29

y is plotted as a function of the row number in the table in the area below the table.a has a toolbar, which is described in Section 3.3. The red dashed horizontal linesshed vertical lines can be dragged to highlight a portion of the plot of interest,en a white background, and the rest is gray. The atoms associated with the high-ion of the plot are interactively selected in the Workspace, and the rows for the

e highlighted region are selected in the table.

t to export the values in the table, click Export or Export All. Export exports theperty table as a text file. Export All exports all property tables as a text file. Bothn a file selector in which you can navigate to the location and name the file.

re 3.2. The Protein Structure Quality Viewer panel, Protein Report tab.


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3.3 Plot ToolbarBoth tabs have graphical displays, for which a toolbar provides some tools for manipulation ofthe plot and for saving an image of the plot. This is a generic toolbar, and some of the actionsmay not be the plot or t

ReRe

BaDis

NeDis

PaPanbutZoDr

CoCo

EdMalinSaSavselCoCobutr Software Release 2014-3

useful in the current context. The panel has a toolbar that you can use to configureo save an image of the plot. The toolbar buttons are described below.

set set the plot to the original pan and zoom settings.

ck play the previous view of the plot in the view history

xt play the next view of the plot in the view history

n/zoom the plot by dragging with the left mouse button, zoom by dragging with the right mouse ton.

om to rectangle ag out a rectangle on the plot to zoom in to that rectangle.

nfigure subplots nfigure the margins and spacing of each plot in the panel.

it axis and curve parameters ke settings for the title, range, labeling, and scale of the axes; the color, style, and width of

es; and the color, style, and size of markers.ve imagee an image of the plot to file. Opens a file selector in which you can browse to a location,

ect the image format, and name the image.py to clipboard py an image of the plot to the clipboard. You can then paste it into another application. This ton is only available in some panels.

Chapter 4


Chapter 4: Analyzing Residue Properties

Identifying may be a usto produce sible surfaceither desiramutated to i

To open the

Before anallating the analyze theWorkspace.and progresBioLuminate 1.6 User Manual 31stable or unstable residues, or residues with desirable or undesirable propertieseful precursor to mutation studies. The Residue Analysis panel analyzes a proteinproperties of the residues, including hydropathy, various energies, solvent-acces-e areas, and rotatable bonds. These properties can be used to identify residues withble properties or undesirable properties, which may suggest residues that could bemprove the protein properties.

Residue Analysis panel choose Tasks Residue Analysis in the main window.

yzing a protein, you should prepare it with the Protein Preparation Wizard. Calcu-energetic properties requires an all-atom structure with bond assignments. To properties of a protein, first display it in the Workspace, and then click Analyze A job is run to calculate energetic properties. This job can take several minutes,s is reported in a bar at the bottom of the panel.

Figure 4.1. The Residue Analysis panel, with results.


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When the job finishes, the table is filled in and the first property is plotted below. You can sortthe table by clicking on the heading of the column you want to sort by. A second click changesthe sort direction. The table columns are described in Table 4.1.

You can expin the file se

To highlighselection sespace.

To examinetion of residthe plot. Yospace, by myou might wof the propejust those dThe toolbarThis is a ge

Table 4.1. P

Column

Residue

Hydropathy

Potential E

Internal En

Interaction

SASA (NonSASA (PolaSASA Rotatable br Software Release 2014-3

ort the table data to a CSV file by clicking Export and then providing the file namelector that opens.

t one or more residues in the Workspace, select the table rows. If you have Fit onlected, the view zooms in (or out) so that these residues occupy most of the Work-

a particular property for all residues, you can make a plot of the property as a func-ue position. Choose the property from the Graph property option menu to displayu can use the plot to select residues in the table and highlight them in the Work-oving the dotted lines to enclose the residues you are interested in. For example,ant to select residues that have significantly larger or significantly smaller values

rties than the average, by moving the upper or the lower red dotted line to encloseata points.

provides tools for manipulation of the plot and for saving an image of the plot.neric toolbar, and some of the actions may not be useful in the current context. The

roperty columns in the Residue Analysis panel.

Description

Residue identity: chain, residue number and insertion code, 3-letter name.

Hydropathy calculated using the Kyte-Doolittle scale [6], normalized by the solvent accessible surface area.

nergy Sum of the residue-based internal energy and the non-bonded interaction energy (vdW, electrostatic) between the residue and the remainder of the sys-tem.

ergy Sum of energies arising from intra-residue bonded interactions (bonds, angles, torsions) and intra-residue non-bonded interactions (vdW, electro-static).

Energy Energy of interaction between this residue and all other atoms.

-polar) Solvent-accessible surface area of nonpolar atoms of this residuer) Solvent-accessible surface area of polar atoms of this residue

Total solvent-accessible surface area of this residue

onds Number of rotatable bonds in this residue


panel has a toolbar that you can use to configure the plot or to save an image of the plot. Thetoolbar buttons are described below.

If you want

Reset Reset the plot to the original pan and zoom settings.

BaDis

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bioluminate user manual

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