Force Field for Peptides and Proteins based on the Classical Drude Oscillator.
Force Field for Peptides and Proteins based on the Classical Drude Oscillator.
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DOI：
10.1021/ct400781b
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发表时间：
2013-12-10
影响因子：
5.5
通讯作者：
MacKerell, Alexander D., Jr.
中科院分区：
文献类型：
--
作者：
Lopes, Pedro E. M.;Huang, Jing;Shim, Jihyun;Luo, Yun;Li, Hui;Roux, Benoit;MacKerell, Alexander D., Jr.
提出了一种基于经典德鲁德振子框架的极化力场，目前已在CHARMM和NAMD程序中实现，用于多肽和蛋白质的建模和分子动力学（MD）模拟研究。以代表蛋白质中官能团的模型化合物参数为基础，重点优化多肽主链参数以及主链与侧链之间的连接。针对短多肽如（Ala）5的量子力学构象能、与水的相互作用、分子偶极矩和极化率以及实验凝聚相数据，优化了主静电参数。对主链φ， ψ构象偏好的优化还包括通过CMAP项对二维样条函数表的调整。该模型的验证包括对一系列多肽和蛋白质的模拟。在显式溶剂MD模拟中，第一代极化模型在100ns时间尺度上保持了所研究体系的折叠态。与加性CHARMM36力场（C36）相比，Drude模型通常产生更大的RMS差异，并且与加性模型相比显示出额外的灵活性。与核磁共振化学位移数据的比较表明，相对于添加剂，极化模型有较小的退化，尽管一致性水平可能被认为是令人满意的，而对于在添加剂模型中显示出明显低估了S2阶参数的残留物，使用极化模型计算了改进。与多肽主链和色氨酸侧链相关的偶极矩分析显示，Drude模型的值明显大于C36模型，多肽主链的偶极矩在片状中比螺旋状中增强得更大，并且在MD模拟过程中观察到单个部分的偶极子发生了显著变化。尽管仍有一些局限性，但所提出的模型，称为Drude-2013，预计将产生肽和蛋白质结构和功能的分子图像，这将以计算可访问的方式增加物理有效性和内部一致性。
Presented is a polarizable force field based on a classical Drude oscillator framework, currently implemented in the programs CHARMM and NAMD, for modeling and molecular dynamics (MD) simulation studies of peptides and proteins. Building upon parameters for model compounds representative of the functional groups in proteins, the development of the force field focused on the optimization of the parameters for the polypeptide backbone and the connectivity between the backbone and side chains. Optimization of the backbone electrostatic parameters targeted quantum mechanical conformational energies, interactions with water, molecular dipole moments and polarizabilities and experimental condensed phase data for short polypeptides such as (Ala)5. Additional optimization of the backbone φ, ψ conformational preferences included adjustments of the tabulated two-dimensional spline function through the CMAP term. Validation of the model included simulations of a collection of peptides and proteins. This 1st generation polarizable model is shown to maintain the folded state of the studied systems on the 100 ns timescale in explicit solvent MD simulations. The Drude model typically yields larger RMS differences as compared to the additive CHARMM36 force field (C36) and shows additional flexibility as compared to the additive model. Comparison with NMR chemical shift data shows a small degradation of the polarizable model with respect to the additive, though the level of agreement may be considered satisfactory, while for residues shown to have significantly underestimated S2 order parameters in the additive model, improvements are calculated with the polarizable model. Analysis of dipole moments associated with the peptide backbone and tryptophan side chains show the Drude model to have significantly larger values than those present in C36, with the dipole moments of the peptide backbone enhanced to a greater extent in sheets versus helices and the dipoles of individual moieties observed to undergo significant variations during the MD simulations. Although there are still some limitations, the presented model, termed Drude-2013, is anticipated to yield a molecular picture of peptide and protein structure and function that will be of increased physical validity and internal consistency in a computationally accessible fashion.
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DOI：
10.1088/0953-8984/21/33/333102
发表时间：
2009-08-19
期刊：
Journal of physics. Condensed matter : an Institute of Physics journal
影响因子：
--
作者：
Cieplak P;Dupradeau FY;Duan Y;Wang J
通讯作者：
Wang J
影响因子：
3.4
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
通讯作者：
Hummer, Gerhard
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
影响因子：
3.3
作者：
Baker, Christopher M.;Anisimov, Victor M.;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.