Implicit Solvents for the Polarizable Atomic Multipole AMOEBA Force Field.
Implicit Solvents for the Polarizable Atomic Multipole AMOEBA Force Field.
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DOI：
10.1021/acs.jctc.0c01286
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发表时间：
2021-04-13
影响因子：
5.5
通讯作者：
Schnieders MJ
中科院分区：
文献类型：
--
作者：
Corrigan RA;Qi G;Thiel AC;Lynn JR;Walker BD;Casavant TL;Lagardere L;Piquemal JP;Ponder JW;Ren P;Schnieders MJ
计算蛋白质设计、从头算蛋白质/RNA折叠和蛋白质-配体筛选对于显式处理溶剂来说可能需要太多的计算。对于这些应用，隐含溶剂提供了一个引人注目的替代方案，我们在这里描述了基于连续介质静力学的三种处理方法的可极化原子多极阿米巴力场：非线性和线性化版本的泊松-玻尔兹曼方程(PBE)的数值解，PBE的区域分解类导体屏蔽模型(DdCOSMO)近似，以及解析的广义Kirkwood(GK)近似。将连续介质静电模型与基于新的空化和色散项的非极性估计器相结合。采用基于103个小分子溶剂化自由能差库的最小二乘法目标函数对静电模型参数进行了数值优化。APBS、ddCOSMO和GK模型的平均有符号误差分别为0.05、0.00和0.00千卡/摩尔，而平均无符号误差分别为0.70、0.63和0.58千卡/摩尔。Tinker(或Tinker-HP)、OpenMM和Force field X软件包中提供的隐式溶剂的静电响应验证是基于与一系列蛋白质和核酸的显式溶剂模拟的比较。总体而言，可极化力场的表演性隐含溶剂模型的出现将为它们在折叠和设计应用中的使用打开大门。
Computational protein design, ab initio protein/RNA folding, and protein-ligand screening can be too computationally demanding for explicit treatment of solvent. For these applications, implicit solvent offers a compelling alternative, which we describe here for the polarizable atomic multipole AMOEBA force field based on three treatments of continuum electrostatics: numerical solutions to the nonlinear and linearized versions the Poisson-Boltzmann equation (PBE), the domain-decomposition Conductor-like Screening Model (ddCOSMO) approximation to the PBE, and the analytic generalized Kirkwood (GK) approximation. The continuum electrostatic models are combined with a nonpolar estimator based on novel cavitation and dispersion terms. Electrostatic model parameters are numerically optimized using a least squares style target function based on a library of 103 small molecule solvation free energy differences. Mean signed errors for the APBS, ddCOSMO, and GK models are 0.05, 0.00, and 0.00 kcal/mol, respectively, while the mean unsigned errors are 0.70, 0.63, and 0.58 kcal/mol, respectively. Validation of the electrostatic response of the resulting implicit solvents, which are available in the Tinker (or Tinker-HP), OpenMM, and Force Field X software packages, is based on comparisons to explicit solvent simulations for a series of proteins and nucleic acids. Overall, the emergence of performative implicit solvent models for polarizable force fields will open the door to their use for folding and design applications.
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影响因子：
6.1
作者：
CONNOLLY, ML
通讯作者：
CONNOLLY, ML
影响因子：
5.5
作者：
Aguilar, Boris;Shadrach, Richard;Onufriev, Alexey V.
通讯作者：
Onufriev, Alexey V.
影响因子：
15
作者：
Chen, Jianhan;Brooks, Charles L., III
通讯作者：
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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：
3.3
作者：
Bernales, Varinia S.;Marenich, Aleksandr V.;Truhlar, Donald G.
通讯作者：
Truhlar, Donald G.