tutorials for protein data bank and swiss pdb viewer
DESCRIPTION
Tutorials for protein data bank and swiss PDB viewer. 2010/04/12 Prof. Jinn-Moon Yang Yen-Fu Chen and Kai-Cheng Hsu. http://140.113.239.67/spv.ppt. Contents. Introduction of protein structures Using thymidine kinase as an example Download and install Tutorial - PowerPoint PPT PresentationTRANSCRIPT
Tutorials for protein data bank and swiss PDB viewer
2010/04/12
Prof. Jinn-Moon Yang
Yen-Fu Chen and Kai-Cheng Hsu
http://140.113.239.67/spv.ppt
Contents
Introduction of protein structuresUsing thymidine kinase as an example
Download and installTutorial
Download protein structures from PDBBasic Operation Advance Operation
Resources for tutorialhttp://www.youtube.com/watch?v=yFE3CAHNkZg&feature=related
Introduction of protein structures
Proteins present in all biological organismsPolymers of amino acids (20 L-α-amino acids)
Nanoparticles
Perform particular biochemical functions
Nature: Mattson, M. Nature. 422, 385-387 (2003)stemcells.nih.go: Early Development
Transcription and translation Cell regulation and catalysis reactions
Introduction of protein structures
To enable to perform protein’s biological function, protein fold into one or more specific spatial conformations driven by noncovalent interactions
Hydrogen bonding, ionic interactions, van der Waals forces and hydrophobic packing
3D protein structures are necessary for understanding the functions of protein at molecular level
Adapted from Protein Structure in Wikipedia
Hemoglobin: oxy-deoxy states
Adapted from structural biology Wikipedia
Protein structure: from amino acid to quaternary structure
Noncovalent interactions for protein structure and function
Ionic bond
A bond formed by the attraction between two oppositely charged ions
Hydrogen bond
An attractive interaction of a hydrogen atom with an electronegative atom, like N,O, and F
Na Cl
Na Cl
Potential energy of Na and Cl Potential energy of Na and Cl
Noncovalent interactions for protein structure and function
van der Waals forceAttractive or repulsive force between molecules
Hydrophobic interactionThe physical property of a molecule (known as a hydrophobe) that is repelled from a mass of water
An example of van der Waals force:Gecko climbs on the glass
An example of hydrophobic interaction:Water drops on hydrophobic surface
Protein structure database:Protein data bank (PDB)
Techniques for determining atomic structures
X-ray crystallography, NMR spectroscopy and electron microscopy
PDB contains information about experimentally-determined structures of biological marcomoleculeas (proteins, and DNA/RNA)
Proteins (1kim)
DNAs/RNAs (2k7e)
Biological complexes (1zrc)
X-ray
NMR
EM
http://www.pdb.org/
Search protein structures in PDB
PDB provides search by protein name, ligand, or structrue related keywords
Search example: thymidine kinase (TK)
• Function: DNA synthesis
• Therapeutic: Anticancer and antivirus drug target
Example: X-ray structures of virus’ thymidine kinase with substrates/inhibitors
Protein name
Source spices
Experimental method
has ligands
Search result of “X-ray structures of virus’ thymidine kinase with substrates/inhibitors”
TK of virus
TK with ligand (substrate)
PDB ID of this structure
X-ray structure
23 structures for these keywords
Structure and related data (1kim)
The citation of this structure
Related data of this structure
The title of this structure
Visualization of biological assembly
Structure and ligand data (1kim)
Ligand in this structure
Structure and sequence data (1kim)Related data of this structure
Sequence ID of 1kim in UniProtKB
Structure classification ID of 1kim
Advance inspection for protein structure: download structure from PDB
1. Save the data on your PC2. Open the file on a structure
viewer program (swiss PDBviewer, pymol, and etc.)
Classification of Drug Development
Protein
(receptor) S
tructu
re
Compound structure Known Unknown
Known
Unknow
n
Structure-based Drug Design (SBDD)
SBDD or de novo design
High-Throughput Screening(HTS)
Compound similarity searchO
O
O
O
O
O
query Similar compounds
OO
DDT 2002
Discovering new leads
Curr. opin. Chem. Biol. 2002, 439
Yellow: virtual screening (SBDD)Blue: high-throughput screening (HTS)
HTSSBDD
• There are more than 5 H-bond donors.
• The molecular weight is over 500.
• The LogP is over 5.
• There are more than 10 H-bond acceptors.
Drugs derived from structure-based approaches
Drug Discovery Today, 10, 895, 2005
Drug Discovery Today, 10, 895, 2005
Tutorial for Swiss PDB viewer
Download and install
Download Swiss PdbViewerhttp://spdbv.vital-it.ch/download.html
Download user guidehttp://spdbv.vital-it.ch/Swiss-PdbViewerManualv3.7.pdf
Tutorial video (English)http://www.youtube.com/watch?v=nYT5qwtfNew&feature=related
http://www.youtube.com/watch?v=yFE3CAHNkZg
Download page
Install and execute swiss pdb viewer
Workspace
Control panel
Layer info
Main window
Viewer
General Terms
Gray: C atomBlue: N atomRed: O atom
Residue Arginine
Side chain
Main chain
Atom radius
ChainSecondary
Structure (Ribbon)
A protein may have multiple chains
Load PDB1
Load PDB2
Move & Rotate Center Zoom
Translate Rotate
Open control panel
control panel
Display or hide residues-for some residues
Press left button of mouse
Display or hide residues-for all residues
Press right button of mouse
Display or hide side chains of residues
Display or hide residue labels
GLU111
Display or hide atom radius
Render in solid 3D
Show secondary structures -Display or hide ribbons
Change color
Visualization of biological assembly-color by chain
Change color by chain-act on Ribbons
Show residue properties-Change color by Type
Type Reisdue Negative ASP
GLUPositive HIS
LYSARG
Polar SERTYRASNTHRGLN
Hydrophobic CYS
METPHEALATRPLEUILEPROVAL
GLY
Show structure flexibility Change color by B-factor
A low B-factor meaning that the position of the atom has been determined with accuracy
High B-factor
Low B-factor
Other color types
Secondary Structure
Selected residues
Relative accessibility
default atom colors
Root mean square between 2 molecules
Analyze protein-ligand interactions-Select ligands (or residues)
Press left button of mouseto select the ligand (THM, thymidine) of 1kim
Identify binding site-Show protein (ribbon) and ligand (stick)
Select residues in the binding site-Neighbors of selected residues
Center selected residues
H-bonds of the binding site-Compute H-bonds
H-bonds between protein and ligand-Show H-bonds of selection
H-bonds between TK and THM-Show residues from selection
Show residue labelPress right button of mouse
1. Q125 recognize the thymine moiety2. Activity was decreased by over
90% if Q125 mutated (Biochemistry, 2000. 39: p. 4105-4111)
van der Waal forces-Stacking interactions
M128 and Y172 sandwich the thymine moiety Stabilize the binding of substrate (JBC, 1999. 274: p. 31967-31973)
Observe the protein surface -Compute Surface
Surface preference
Show ligand in the surface
Discard surface
Comparison of multiple structures-Import PDB
PDB code: 3vtkAnother structure of thymidine kinase
Open layer info
1kim
3vtk
Show or hide
Superimpose two molecules
Results of superimposition
RMS: 0.63 ǺMeasure the structure similarity
Comparison of binding sites-Neighbors of selected residues
Comparison of ligands
HO O
HO
N ONH
O
HO
OO
PO
HO
HO
N
I
ONH
O
1kim: substrate(CPK)3vtk: inhibitor (Green)
Save files
Homework
Keyword1. How many structures of N1 neuraminidase with ligand ?
2. Capture a picture of N1 neuraminidase (ribbon) and its ligand (stick)
3. Capture a picture of H-bonds between protein and ligand
Mail title: 學號姓名 _HW1_第一題答案的數字