Reparametrization of Protein Force Field Nonbonded Interactions Guided by Osmotic Coefficient Measurements from Molecular Dynamics Simulations.
Reparametrization of Protein Force Field Nonbonded Interactions Guided by Osmotic Coefficient Measurements from Molecular Dynamics Simulations.
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DOI：
10.1021/acs.jctc.6b01059
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发表时间：
2017-04-11
影响因子：
5.5
通讯作者：
Elcock AH
中科院分区：
文献类型：
--
作者：
Miller MS;Lay WK;Li S;Hacker WC;An J;Ren J;Elcock AH
有一个小的，但越来越多的文献描述了使用渗透系数测量来验证和重新参数化模拟力场。在这里，我们已经调查了五个非常常用的力场和水模型组合的能力，以重现七个中性氨基酸和五个小分子的渗透系数。测试的力场包括AMBER ff 99 SB-ILDN、CHARMM 36、GROMOS 54 a7和OPLS-AA，其中第一个力场与TIP 3 P和TIP 4P-Ew水模型一起测试。一般来说，对于氨基酸和小分子，测试力场产生的计算渗透系数低于实验，这是过度有利的溶质-溶质相互作用的指示。当应用于氨基酸时，GROMOS 54 a7提供了这种总趋势的唯一例外：在这种情况下，计算的渗透系数始终过高。重要的是，我们表明，所有的力场测试，可以准确地再现实验渗透系数的氨基酸时，微小的修改-一些以前报道的其他人和一些新的这项研究-进行了货车德瓦尔斯相互作用的带电端基。然而，当用许多力场模拟脯氨酸时需要特别注意，并且当用AMBER ff 99 SB-ILDN模拟时，需要进行羟基特定修饰以校正丝氨酸和苏氨酸。有趣的是，另一种参数化的货车德瓦尔斯相互作用在后者的力场，提出了由Nerenberg和头戈登组，显示出立即产生渗透系数，是非常符合实验。总体而言，这项研究加强了这样的想法，渗透系数的测量可以用来识别一般的缺点，在常用的力场的溶质-溶质相互作用的描述，并进一步表明，修改货车范德华参数提供了一个简单的路线，以优化协议与实验。
There is a small, but growing, body of literature describing the use of osmotic coefficient measurements to validate and reparameterize simulation force fields. Here we have investigated the ability of five very commonly used force field and water model combinations to reproduce the osmotic coefficients of seven neutral amino acids and five small molecules. The force fields tested include AMBER ff99SB-ILDN, CHARMM36, GROMOS54a7, and OPLS-AA, with the first of these tested in conjunction with the TIP3P and TIP4P-Ew water models. In general, for both the amino acids and the small molecules, the tested force fields produce computed osmotic coefficients that are lower than experiment; this is indicative of excessively favorable solute-solute interactions. The sole exception to this general trend is provided by GROMOS54a7 when applied to amino acids: in this case, the computed osmotic coefficients are consistently too high. Importantly, we show that all of the force fields tested can be made to accurately reproduce the experimental osmotic coefficients of the amino acids when minor modifications – some previously reported by others and some that are new to this study – are made to the van der Waals interactions of the charged terminal groups. Special care is required, however, when simulating Proline with a number of the force fields, and a hydroxyl-group specific modification is required in order to correct Serine and Threonine when simulated with AMBER ff99SB-ILDN. Interestingly, an alternative parameterization of the van der Waals interactions in the latter force field, proposed by the Nerenberg and Head-Gordon groups, is shown to immediately produce osmotic coefficients that are in excellent agreement with experiment. Overall, this study reinforces the idea that osmotic coefficient measurements can be used to identify general shortcomings in commonly used force fields’ descriptions of solute-solute interactions, and further demonstrates that modifications to van der Waals parameters provides a simple route to optimizing agreement with experiment.
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影响因子：
5.5
作者：
Andrews, Casey T.;Elcock, Adrian H.
通讯作者：
Elcock, Adrian H.
影响因子：
3.8
作者：
Coffman, RE;Kildsig, DO
通讯作者：
Kildsig, DO
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
DOI：
10.1039/c0cp00111b
发表时间：
2010-07-28
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Dupradeau FY;Pigache A;Zaffran T;Savineau C;Lelong R;Grivel N;Lelong D;Rosanski W;Cieplak P
通讯作者：
Cieplak P