TSRI Administrative CoreIan WilsonPeter KuhnMarc ElsligerFrank von DelftTina MontgomeryGye Won HanRong ChenAngela Walker

UCSD Bioinformatics CoreJohn WooleyAdam GodzikSusan TaylorSlawomir Grzechnik Bill WestAndrew MorseJie QuyangXianhong WangJaume CanavesLukasz JaroszewskiRobert SchwarzenbacherMarc Robinson RechaviChris EdwardsOlga KirillovaRay Bean, Josie Alaoen

Stanford /SSRLStructure Determination CoreKeith HodgsonAshley DeaconBritt HedmanHsiu-Ju ChiuMitchell D. MillerHenry van den BedemQingping XuHerbert AxelrodChristopher RifeKevin JinSilvya OommachenAmanda PradoRon ReyesIrimpan MathewsR. Paul PhizackerleyMichael Solits

GNF & TSRICrystallomics CoreRay Stevens Scott LesleyRebbeca Page Carina GrittiniGlen Spraggon Andreas Kreusch Michael DiDonato Daniel McMullan Heath Klock Polat Abdubek Eileen Ambing Tanya Biorac Joanna C. Hale Justin Haugen Mike HornsbyEric Koesema Edward Nigoghossian Kevin Quijano Megan Wemmer Aprilfawn White Juli VincentJeff VelasquezKin MoyVandana SridharBernard CollinsThomas Clayton

Scientific Advisory BoardCarl-Ivar Brändén,

Karolinska Inst., Stockholm (retired 2003)Elbert Branscomb,

DOE Joint Genome Inst., Walnut CreekStephen Cusack,

EMBL – Outstation GrenobleLeroy Hood,

Inst. for Systems Biology, SeattleJohn Kuriyan, U.C. Berkeley

Erkki Ruoslahti, The Burnham Institute

James Wells, Sunesis Pharmaceuticals, Inc.

Charles Cantor. Sequenom, Inc.Todd Yeates,

UCLA-DOE, Inst. for Genomics and ProteomicsJames Paulson,

Consortium for Functional Glycomics,The Scripps Research Institute

Exploratory ProjectsKurt Wüthrich (NMR)Linda ColumbusTouraj Etezady-EsfarjaniWolfgang PetiVirgil Woods (DXMS)

Acknowledgements

NIH Protein Structure Initiative Grant P50 GM62411

The JCSG is funded by the Protein Structure Initiative of the National Institutes of Health, National Institute of General Medical Sciences.SSRL operations is funded by DOE BES, and the SSRL Structural Molecular Biology program by DOE BER, NIH NCRR BTP and NIH NIGMS.

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Mosflm HKL2000 XDS

Percent of residues built for 44 datasets using 3 different processing strategies Percent of residues built by ARP/wARP using 3 different processing strategies

Using REFMAC without phase restrain is statistically significant better (Paired t-Test p<0.01)

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collect 2w+1w collect 3w

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model 1w

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model 3w

Best model for different wavelength combinations of 3 wavelength MAD datasets

Two different data collection strategies for 3 wavelength MAD.

New workflow for Crystallographer

Instead of trying to find the structure solution with an iterative approach,

1.) Provide one time all fundamental information about the data collection

2.) Run all possible processing strategies in parallel without any human intervention

3.) Evaluate the results to determine the best solution

Conclusion

Mosflm-Solve-ResolveMosflm-Sharp-ResolveHKL2000-Solve-ResolveHKL2000-Sharp-Resolve

XDS-Solve-ResolveXDS-Sharp-ResolveMosflm-Solve-w ARPMosflm-Sharp-w ARPHKL2000-Solve-w ARP

HKL2000-Sharp-w ARPXDS-Solve-w ARP

XDS-Sharp-w ARP

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TM1410 p21 2.5Å

TM0816 c2 2.7Å

TM0312 p21 2.6Å

TM1586 p3121 2.0Å

TM0559 h3 2.5Å

TM0796 p4123 2.9Å

TM0119 p212121 2.7Å

TM1030 p21 2.5Å

TB0251L c2221 2.1Å

TM0755 p21 1.9Å

TB0723G p212121 2.2Å

TM0874 c222 2.7Å

TM1622 p3221 1.9Å

MM2105A p31 2.2Å

TM1436 p6422 2.1Å

EC5318A p212121 1.8Å

TB0723G p212121 2.0Å

TB0885A p6322 1.4Å

TB1568L p3121 2.6Å

TB0885A p6322 2.8Å

XB5713A p6522 2.2Å

MB2347A i422 1.6Å

XB5607A p4212 2.4Å

TM1224 p3112 3.0Å

TB0176B p212121 2.8Å

TM0892 i222 2.3Å

TB1363E p43212 2.8Å

TM0922 i422 2.9Å

TM0922 i422 2.8Å

TM1380 p212121 2.4Å

10174951 p21 1.9Å

TM1553 p212121 1.6Å

TB5103A p63 2.7Å

TB3399M p212121 2.3Å

TM0378 p21 2.1Å

MB2013A p212121 1.8Å

IB2347B p212121 2.4Å

TM1367 p21212 2.0Å

TM0894 p212121 2.2Å

IB3841A p6 2.1Å

TB1783C p41212 2.2Å

TB0541B p43 1.8Å

XB5512A c2 1.3Å

MB2347A i422 2.2Å

Percent of residues built for 44 datasets using 12 different processing strategies

Xsolve is already a valuable component of the JCSG high-throughput structure determination pipeline.

Xsolve supports a non-iterative workflow for crystallographers by trying all possible solutions in parallel.

None of the processing strategies outperforms the others for all datasets.However they are often complementing each other and Xsolve can maximize the number of automatically built residues by running several processing strategies in parallel.

Xsolve is open for extensions with additional crystallography programs.

The first Xsolve version for public release will be available in November 2005.Xsolve will be available for some of the SSRL users outside of JCSG with the start of the next run at SSRL in November 2005.

Xsolve Processing Steps

• Create working directory (e.g. resolve/p3221/nmol1/lambda12 )

• Assemble input.xml files (e.g. from target.xml, scale.xml, solve.xml)

• Copy input files to work directory (e.g. solve.mtz, ha.pdb)

• XSLT to create shell script (e.g. input_resolve.xml -> resolve.csh)

• Execute shell script (e.g. resolve.csh)

• Monitor execution (error messages, timeout, file size limits,…)

• Parse log file (e.g. resolve.log -> resolve.xml)

CollectData.xmlTrace.xml