Blind prediction of interfacial water positions in CAPRI.

TitleBlind prediction of interfacial water positions in CAPRI.
Publication TypeJournal Article
Year of Publication2014
AuthorsLensink, M. F., I. H. Moal, P. A. Bates, P. L. Kastritis, A. S. J. Melquiond, E. Karaca, C. Schmitz, M. van Dijk, A. M. J. J. Bonvin, M. Eisenstein, B. Jiménez-García, S. Grosdidier, A. Solernou, L. Pérez-Cano, C. Pallara, J. Fernández-Recio, J. Xu, P. Muthu, K. Praneeth Kilambi, J. J. Gray, S. Grudinin, G. Derevyanko, J. C. Mitchell, J. Wieting, E. Kanamori, Y. Tsuchiya, Y. Murakami, J. Sarmiento, D. M. Standley, M. Shirota, K. Kinoshita, H. Nakamura, M. Chavent, D. W. Ritchie, H. Park, J. Ko, H. Lee, C. Seok, Y. Shen, D. Kozakov, S. Vajda, P. J. Kundrotas, I. A. Vakser, B. G. Pierce, H. Hwang, T. Vreven, Z. Weng, I. Buch, E. Farkash, H. J. Wolfson, M. Zacharias, S. Qin, H-X. Zhou, S-Y. Huang, X. Zou, J. A. Wojdyla, C. Kleanthous, and S. J. Wodak
JournalProteins
Volume82
Issue4
Pagination620-32
Date Published2014 Apr
ISSN1097-0134
KeywordsAlgorithms, Colicins, Computational Biology, Models, Molecular, Molecular Docking Simulation, Protein Conformation, Protein Interaction Mapping, Water
Abstract

We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 Å, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes.

DOI10.1002/prot.24439
Alternate JournalProteins
PubMed ID24155158
Grant List10748 / / Cancer Research UK / United Kingdom
BB/G020671/2 / / Biotechnology and Biological Sciences Research Council / United Kingdom
GG/G020671/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 GM061867 / GM / NIGMS NIH HHS / United States
R01 GM064700 / GM / NIGMS NIH HHS / United States
R01GM074255 / GM / NIGMS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
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