28 Mar 06Automation1 Overview of developments within CCP4 Generation 1 ccp4i tasks Generation 2 isolated scripts / web service Generation 3 integrated environment

28 Mar 06Automation2 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

28 Mar 06Automation3 Mr Bump in pictures

28 Mar 06Automation4 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

28 Mar 06Automation5 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

28 Mar 06Automation6 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

28 Mar 06Automation7 HAPPy details - outputs HL coefficients - density modification using DM and pirate Test on ccp4cluster Experimental and synthetic test data

28 Mar 06Automation8 Experimental Phasing - CRANK (assoc.) Steven Ness, Raj Pannu (Leiden University) - –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 version does not include crunch2

28 Mar 06Automation9 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)

28 Mar 06Automation10 XIA-DPA - what does it do? Index Integrate Determine point group Scale Merge Analyse Using a variety of programs…

28 Mar 06Automation11 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

28 Mar 06Automation12 Future Challenges Model Building –Buccaneer (KC) –Ligands (PE) Generation 3 – Integration of automation efforts – Communication – Customisation – Feedback and Display