Coupling Monte Carlo, Variational Implicit Solvation, and Binary Level-Set for Simulations of Biomolecular Binding.
Coupling Monte Carlo, Variational Implicit Solvation, and Binary Level-Set for Simulations of Biomolecular Binding.
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DOI：
10.1021/acs.jctc.0c01109
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发表时间：
2021-04-13
影响因子：
5.5
通讯作者：
McCammon JA
中科院分区：
文献类型：
--
作者：
Zhang Z;Ricci CG;Fan C;Cheng LT;Li B;McCammon JA
我们开发了一种混合的方法，结合蒙特卡罗（MC）方法，变分隐式溶剂模型（VISM），和一个二元水平集方法模拟生物分子结合在水溶剂中。的生物分子复合物的溶剂化自由能估计通过最小化的VISM自由能功能的所有可能的溶质-溶剂界面，用作介电边界。该泛函由溶质体积能、溶质-溶剂界面能、溶质-溶剂货车范德华相互作用能和静电自由能组成。一种技术的移动的介电边界被用来准确地预测溶剂化自由能的静电部分。最小化这样的功能，在每个MC移动是可能的，我们的新的和快速的二进制水平集方法。该方法是基于近似的表面积的卷积的指示函数与compounds支持的内核，并通过简单的翻转的数值网格单元局部周围的溶质-溶剂界面。我们将我们的方法应用于p53-MDM 2系统，其中两个分子近似为刚体。我们有效的方法捕获了一些姿势之前的最终绑定状态。全原子分子动力学模拟大多数这样的姿态很快达到最终的束缚态。我们的工作是朝着生物分子相互作用的真实模拟迈出的新一步。随着粗粒化和MC采样的进一步改进，并与其他模型相结合，我们的混合方法可用于研究配体与蛋白质结合的自由能景观和动力学途径。
We develop a hybrid approach that combines the Monte Carlo (MC) method, a variational implicit-solvent model (VISM), and a binary level-set method for the simulation of biomolecular binding in an aqueous solvent. The solvation free energy for the biomolecular complex is estimated by minimizing the VISM free-energy functional of all possible solute-solvent interfaces that are used as dielectric boundaries. This functional consists of the solute volumetric, solute-solvent interfacial, solute-solvent van der Waals interaction, and electrostatic free energy. A technique of shifting the dielectric boundary is used to accurately predict the electrostatic part of the solvation free energy. Minimizing such a functional in each MC move is made possible by our new and fast binary level-set method. This method is based on the approximation of surface area by the convolution of an indicator function with a compactly supported kernel, and is implemented by simple flips of numerical grid cells locally around the solute-solvent interface. We apply our approach to the p53-MDM2 system for which the two molecules are approximated by rigid bodies. Our efficient approach captures some of the poses before the final bound state. All-atom molecular dynamics simulations with most of such poses quickly reach to the final bound state. Our work is a new step toward realistic simulations of biomolecular interactions. With further improvement of coarse graining and MC sampling, and combined with other models, our hybrid approach can be used to study the free-energy landscape and kinetic pathways of ligand binding to proteins.
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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：
Cheng, Li-Tien;Xie, Yang;Dzubiella, Joachim;McCammon, J. Andrew;Che, Jianwei;Li, Bo
通讯作者：
Li, Bo
DOI：
10.1021/acs.jpcb.7b04113
发表时间：
2017-07-13
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Ricci CG;Li B;Cheng LT;Dzubiella J;McCammon JA
通讯作者：
McCammon JA
影响因子：
15
作者：
Chen, Jianhan;Brooks, Charles L., III
通讯作者：
Brooks, Charles L., III
影响因子：
15
作者：
Chen, Hai-Feng;Luo, Ray
通讯作者：
Luo, Ray