AUTOMATED FORCE FIELD PARAMETERIZATION FOR NON-POLARIZABLE AND POLARIZABLE ATOMIC MODELS BASED ON AB INITIO TARGET DATA.
AUTOMATED FORCE FIELD PARAMETERIZATION FOR NON-POLARIZABLE AND POLARIZABLE ATOMIC MODELS BASED ON AB INITIO TARGET DATA.
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DOI：
10.1021/ct4003477
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发表时间：
2013-08-13
影响因子：
5.5
通讯作者：
Roux, Benoit
中科院分区：
文献类型：
--
作者：
Huang, Lei;Roux, Benoit
基于原子模型的经典分子动力学（MD）模拟越来越多地用于研究广泛的生物系统。从这样的模拟有意义的结果的先决条件是一个准确的分子力学力场。目前大多数生物分子模拟都基于广泛使用的ABER和CHARMM力场，这些力场经过参数化和优化，以覆盖与天然氨基酸和核酸碱基对应的一小部分基本化合物。附加化合物的原子模型通常通过类比给定力场的参数集来生成。虽然该过程产生内部一致的模型，但是所产生的模型的准确性可能是有限的。在这项工作中，我们提出了一种方法，通用自动原子模型参数化（GAAMP），自动生成的原子模型的参数的小分子从头计算（QM）的计算结果作为目标数据。先前为各种模型化合物开发的力场用作初始猜测，尽管任何最终参数都可以优化。的静电参数（部分电荷，极化率和屏蔽）的基础上优化的QM静电势（ESP），如果适用的话，化合物和水分子之间的相互作用能。软二面角自动识别和参数化的目标QM二面角扫描以及稳定的构象的能量。为了验证该方法，溶剂化自由能的计算超过200个小分子和分子动力学模拟3种不同的蛋白质进行。
Classical molecular dynamics (MD) simulations based on atomistic models are increasingly used to study a wide range of biological systems. A prerequisite for meaningful results from such simulations is an accurate molecular mechanical force field. Most biomolecular simulations are currently based on the widely used AMBER and CHARMM force fields, which were parameterized and optimized to cover a small set of basic compounds corresponding to the natural amino acids and nucleic acid bases. Atomic models of additional compounds are commonly generated by analogy to the parameter set of a given force field. While this procedure yields models that are internally consistent, the accuracy of the resulting models can be limited. In this work, we propose a method, General Automated Atomic Model Parameterization (GAAMP), for generating automatically the parameters of atomic models of small molecules using the results from ab initio quantum mechanical (QM) calculations as target data. Force fields that were previously developed for a wide range of model compounds serve as initial guess, although any of the final parameter can be optimized. The electrostatic parameters (partial charges, polarizabilities and shielding) are optimized on the basis of QM electrostatic potential (ESP) and, if applicable, the interaction energies between the compound and water molecules. The soft dihedrals are automatically identified and parameterized by targeting QM dihedral scans as well as the energies of stable conformers. To validate the approach, the solvation free energy is calculated for more than 200 small molecules and MD simulations of 3 different proteins are carried out.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
4.4
作者：
FELLER, SE;ZHANG, YH;BROOKS, BR
通讯作者：
BROOKS, BR
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
DOI：
10.1085/jgp.201210827
发表时间：
2012-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Lacroix JJ;Pless SA;Maragliano L;Campos FV;Galpin JD;Ahern CA;Roux B;Bezanilla F
通讯作者：
Bezanilla F