Improving 3D structure prediction from chemical shift data
We report advances in the calculation of protein structures from chemical shift nuclear magnetic resonance data alone. Our previously developed method, CS-Rosetta, assembles structures from a library of short protein fragments picked from a large library of protein structures using chemical shifts and sequence information. Here we demonstrate that combination of a new and improved fragment picker and the iterative sampling algorithm RASREC yield significant improvements in convergence and accuracy. Moreover, we introduce improved criteria for assessing the accuracy of the models produced by the method. The method was tested on 39 proteins in the 50–100 residue size range and yields reliable structures in 70 % of the cases. All structures that passed the reliability filter were accurate (<2 Å RMSD from the reference).
KeywordsNuclear magnetic resonance Protein structure calculation CS-ROSETTA Sparse data
This work was supported by the German Science Foundation (DFG) Grant LA 1817/3-1 (to Z.Z. and O.F.L.), the Brussels Institute for Research and Innovation (Innoviris) grant BB2B 2010-1-12 (to W.F.V.), and the Intramural Research Program of the NIDDK (to Y.S.). The WeNMR project (European FP7 e-Infrastructure Grant, Contract No. 261572, www.wenmr.eu), supported by the European Grid Initiative (EGI) through the national GRID Initiatives of Belgium, France, Italy, Germany, the Netherlands (via the Dutch BiG Grid project), Portugal, Spain, UK, South Africa, Malaysia, Taiwan and the Latin America GRID infrastructure via the Gisela project is acknowledged for the use of web portals, computing and storage facilities.
- Lange OF, Rossi P, Sgourakis NG, Song Y, Lee H-W, Aramini JM, Ertekin A, Xiao R, Acton TB, Montelione GT et al (2012) Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples. Proc Natl Acad Sci USA 109:10873–10878ADSCrossRefGoogle Scholar
- Rieping W, Vranken WF (2010) Validation of archived chemical shifts through atomic coordinates. Proteins 78:2482–2489Google Scholar
- Schmitz C, Vernon R, Otting G, Baker D, Huber T (2012) Protein structure determination from pseudocontact shifts using ROSETTA. J Mol Biol 416(5):668–677Google Scholar
- Sheffler W, Baker D (2008) RosettaHoles: rapid assessment of protein core packing for structure prediction, refinement, design and validation. Protein Sci 18(1):229–239Google Scholar
- Wassenaar TA, van Dijk M, Loureiro-Ferreira N (2012) WeNMR: structural biology on the grid. J Grid 10:743–767Google Scholar