28 mar 06automation1 overview of developments within ccp4 generation 1 ccp4i tasks generation 2...

28 Mar 06 Automation 1

Overview of developments within CCP4

Generation 1• ccp4i tasks

Generation 2• isolated scripts / web service

Generation 3 • integrated environment


Molecular Replacement - Mr Bump

• Ronan Keegan and Martyn Winn (DL)• automated framework for Molecular Replacement• Paricular emphasis on generating variety of search models

• Wraps Phaser, Molrep and Amore (Norman Stein)• Uses a variety of helper applications (eg Chainsaw) and bioinformatics tools (eg FASTA, Mafft)• Uses on-line databases (eg PDB, Scop)

• In favourable cases, gives “one-button” solution• In unfavourable cases, suggests likely search models for manual investigation


Mr Bump in pictures

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.




• Model generation- initial search for homologues based upon fasta search of PDB (can be run locally)- template list based upon single chains, domains and multimers- optional side chain pruning by Chainsaw or molrep

• MR engine- choice of Phaser, molrep or amore.

• Success or failure- based upon Rfree in refinement of solution

• Performance- July 05 testing on SPINE targets, worked well on straightforward solutions- brute force method, so compute power important

Mr Bump details and performance


Molecular Replacement - MMASS

• Authors: Garib Murshudov, Alexei Vagin, Fei Long (YSBL)

• Built around molrep MR and model preparation, refmac and sfcheck• Custom database• Manager control process• Protocols

– Simple molecular replacement– Domains iterated with refinement– Use of tertiary structure if available– Completion of MR using phased MR and refinement

• Extensive testing against PDB

• Good performance against SPINE test data


Experimenal Phasing - HAPPy

• Paul Emsley (York University), Daniel Rolfe (DL), Charles Ballard (DL)



• son of CHART, written in python

- SAD implemented

- custom analysis for resolution

range from scala and fhscal

- initially uses shelxd for at location,

with acorn to follow (?)

- phasing using mlphare, bp3 or

phaser


HAPPy details

- outputs HL coefficients

- density modification using DM and pirate

• Test on ccp4cluster

• Experimental and synthetic test data










Experimental Phasing - CRANK (assoc.)

• Steven Ness, Raj Pannu (Leiden University)- www.bfsc.leidenuniv.nl/software/crank/index.html– Contact authors for more information

• Written in TCL/TK and interface tightly with CCP4i.• SAD/MAD heavy atom phasing• Built around BP3 and maximum likelihood techniques

Unfortunately, the ccp4 versiondoes not include crunch2


Data processing - XIA-DPA (assoc.)

• Author Graeme Winter (DL)

• XIA-DPA is an automated system to process and analyse X-Ray diffractions data

• Designed to fill the gap between DNA and CCP4 (automation)• Produces output in standard format files• Includes 2D and 3D pipelines for processing,

via Mosflm/Scala and XDS/XSCALE(/Scala)QuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture.


XIA-DPA - what does it do?

• Index• Integrate• Determine point group• Scale• Merge• Analyse

Using a variety of programs…




CCP4i database backend

• Authors: Peter Briggs, Wendy Yang

• Implemented using SQLlite and python• Automation means lots of data

– Process tracking– Data tracking– persistence of data

• Collaborating closely with HAPPy and XIA-DPA• Integration with ccp4i database handler is

beginning






Future Challenges

• Model Building– Buccaneer (KC)– Ligands (PE)

• Generation 3– Integration of automation efforts

– Communication– Customisation– Feedback and Display

28 mar 06automation1 overview of developments within ccp4 generation 1 ccp4i tasks generation 2...

Documents

phased mr

availablecompletion

variety of search models

molrep mr engine choice

fasta search of pdb

likely search models

ccp4i database handler

pdbgood performance