Blind prediction of interfacial water positions in CAPRI.
Blind prediction of interfacial water positions in CAPRI.
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DOI：
10.1002/prot.24439
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发表时间：
2014-04
期刊：
影响因子：
2.9
通讯作者：
Wodak SJ
中科院分区：
文献类型：
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作者：
Lensink MF;Moal IH;Bates PA;Kastritis PL;Melquiond AS;Karaca E;Schmitz C;van Dijk M;Bonvin AM;Eisenstein M;Jiménez-García B;Grosdidier S;Solernou A;Pérez-Cano L;Pallara C;Fernández-Recio J;Xu J;Muthu P;Praneeth Kilambi K;Gray JJ;Grudinin S;Derevyanko G;Mitchell JC;Wieting J;Kanamori E;Tsuchiya Y;Murakami Y;Sarmiento J;Standley DM;Shirota M;Kinoshita K;Nakamura H;Chavent M;Ritchie DW;Park H;Ko J;Lee H;Seok C;Shen Y;Kozakov D;Vajda S;Kundrotas PJ;Vakser IA;Pierce BG;Hwang H;Vreven T;Weng Z;Buch I;Farkash E;Wolfson HJ;Zacharias M;Qin S;Zhou HX;Huang SY;Zou X;Wojdyla JA;Kleanthous C;Wodak SJ
我们报告了对蛋白质 - 蛋白质界面上水位位置的首次评估，作为CAPRI的一部分（对预测相互作用的批判性评估）社区范围的实验。 IM2免疫蛋白（CAPRI靶标47）被邀请使用其选择的方法来预测界面水分子的位置。总共有195个模型 - 通过测量176个高质量对接模型的水介导的蛋白质接触的召回率。高于0.5的6％。总体上，准确的水平不超过1.5Å，即使在良好的模型中，大约一半的触点代表了误报尽管如此，三个热点界面的水位置得到了很好的预测，因此，据信稳定循环的水位置之一，这些循环在这些络合物中的特异性总体上是最佳的界面水预测。模型表明蛋白质部分的准确建模是确定的因素。从这种分析中获得的见解似乎也有助于改善蛋白质 - 水相互作用的预测及其在稳定蛋白质复合物中的作用。
We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the CAPRI (Critical Assessment of Predicted Interactions) 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.