Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking discrimination.
Efficient consideration of coordinated water molecules improves computational protein-protein and protein-ligand docking discrimination.
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DOI：
10.1371/journal.pcbi.1008103
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发表时间：
2020-09
影响因子：
4.3
通讯作者：
DiMaio F
中科院分区：
文献类型：
--
作者：
Pavlovicz RE;Park H;DiMaio F
高度配位的水分子经常是蛋白质-蛋白质和蛋白质-配体界面的组成部分。我们引入了一个更新的能量模型，该模型有效地捕捉了这些有序水分子在蛋白质表面的能量效应。提出了一种两步法，首先确定以适合放置水的几何形状排列的极性基团，然后使用改进的蒙特卡罗模拟方法将高度配位的水放置在蛋白质表面，同时采样氨基酸侧链取向。这种“半显式”水模型在Rosetta中实现，既适用于结构预测，也适用于蛋白质设计。我们发现，我们的新方法和能量模型在蛋白质-蛋白质天然结构恢复和蛋白质-配体对接识别测试中都有显着的改进。配位良好的水分子-那些与附近的极性基团形成多个氢键的分子-在生物分子系统的结构中扮演着重要的角色，但在分子能量计算中往往不考虑这些水的影响。在这篇文章中，我们描述了一种有效地考虑这些水分子的方法，包括隐式和显式地考虑由两个极性分子形成的界面。在与确定蛋白质如何与结合伙伴相互作用的计算中，我们表明这种新方法的使用显著改善了结果。未来这种方法的应用可能会改进新的蛋白质和小分子药物的设计。
Highly coordinated water molecules are frequently an integral part of protein-protein and protein-ligand interfaces. We introduce an updated energy model that efficiently captures the energetic effects of these ordered water molecules on the surfaces of proteins. A two-stage method is developed in which polar groups arranged in geometries suitable for water placement are first identified, then a modified Monte Carlo simulation allows highly coordinated waters to be placed on the surface of a protein while simultaneously sampling amino acid side chain orientations. This “semi-explicit” water model is implemented in Rosetta and is suitable for both structure prediction and protein design. We show that our new approach and energy model yield significant improvements in native structure recovery of protein-protein and protein-ligand docking discrimination tests. Well-coordinated water molecules—those forming multiple hydrogen bonds with nearby polar groups—play an important role in the structure of biomolecular systems, yet the effect of these waters is often not considered in molecular energy computations. In this paper, we describe a method to efficiently consider these water molecules both implicitly and explicitly at the interfaces formed by two polar molecules. In computations related to determining how a protein interacts with binding partners, we show that the use of this new method significantly improves results. Future application of this approach may improve the design of new protein and small molecule drugs.
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影响因子：
2.9
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
通讯作者：
Wodak SJ
影响因子：
5.5
作者：
Beauchamp, Kyle A.;Lin, Yu-Shan;Das, Rhiju;Pande, Vijay S.
通讯作者：
Pande, Vijay S.
影响因子：
5.5
作者：
O'Meara, Matthew J.;Leaver-Fay, Andrew;Tyka, Michael D.;Stein, Amelie;Houlihan, Kevin;DiMaio, Frank;Bradley, Philip;Kortemme, Tanja;Baker, David;Snoeyink, Jack;Kuhlman, Brian
通讯作者：
Kuhlman, Brian
影响因子：
3.3
作者：
Li, Z;Lazaridis, T
通讯作者：
Lazaridis, T
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE