如何在蛋白质力场中达到构象平衡以进行分子动力学模拟？,Wiley Interdisciplinary Reviews: Computational Molecular Science

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如何在蛋白质力场中达到构象平衡以进行分子动力学模拟？
Wiley Interdisciplinary Reviews: Computational Molecular Science ( IF 16.8 ) Pub Date : 2021-10-05 , DOI: 10.1002/wcms.1578
Wei Kang ₁ , Fan Jiang ₂ , Yun‐Dong Wu _{1,

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Affiliation

分子动力学 (MD) 模拟是探索蛋白质构象能量景观的有力工具，MD 结果的可靠性关键取决于潜在的力场 (FF)。能够在多个层次上产生不同构象的平衡分布的准确 FF 一直是一个长期追求的目标。为此，已经进行了几十年的共同努力来解决 FF 缺陷，表现为不同水平的构象偏差（局部构象、二级结构和多肽链的全局延伸）。我们首先介绍主要的 FF 偏差，然后回顾分别解决它们的策略。具体来说，扭转参数优化的非残基特异性和残基特异性策略均已应用于实现局部构象和二级结构平衡。使用特定于残基的扭转参数可以获得显着的改进，特别是在考虑显式二面耦合时。此外，蛋白质-蛋白质和蛋白质-水相互作用之间的额外平衡已通过多种方式进行优化，以重现多肽链的全局延伸性，特别是对于未折叠或无序的蛋白质。这篇综述旨在总结过去最有价值的经验和教训，我们希望这可以促进经典 FF 和更复杂的模型（如可极化 FF）的进一步改进。使用特定于残基的扭转参数可以获得显着的改进，特别是在考虑显式二面耦合时。此外，蛋白质-蛋白质和蛋白质-水相互作用之间的额外平衡已通过多种方式进行优化，以重现多肽链的全局延伸性，特别是对于未折叠或无序的蛋白质。这篇综述旨在总结过去最有价值的经验和教训，我们希望这可以促进经典 FF 和更复杂的模型（如可极化 FF）的进一步改进。使用特定于残基的扭转参数可以获得显着的改进，特别是在考虑显式二面耦合时。此外，蛋白质-蛋白质和蛋白质-水相互作用之间的额外平衡已通过多种方式进行优化，以重现多肽链的全局延伸性，特别是对于未折叠或无序的蛋白质。这篇综述旨在总结过去最有价值的经验和教训，我们希望这可以促进经典 FF 和更复杂的模型（如可极化 FF）的进一步改进。特别是对于未折叠或无序的蛋白质。这篇综述旨在总结过去最有价值的经验和教训，我们希望这可以促进经典 FF 和更复杂的模型（如可极化 FF）的进一步改进。特别是对于未折叠或无序的蛋白质。这篇综述旨在总结过去最有价值的经验和教训，我们希望这可以促进经典 FF 和更复杂的模型（如可极化 FF）的进一步改进。

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How to strike a conformational balance in protein force fields for molecular dynamics simulations?

Molecular dynamics (MD) simulation is a powerful tool for exploring the conformational energy landscape of proteins, and the reliability of MD results is crucially dependent on the underlying force field (FF). An accurate FF capable of producing balanced distributions of diverse conformations at multiple levels has been a long-sought goal. Towards this, several decades of joint efforts have been made to address FF deficiencies, manifested by conformational biases at different levels (local conformations, secondary structures, and global extendedness of polypeptide chain). We first present the major FF biases, then review the strategies to address them separately. Specifically, both nonresidue-specific and residue-specific strategies for torsional parameter optimization have been applied to achieve local conformation and secondary structure balances. Significant improvements can be gained with residue-specific torsional parameters especially when explicit dihedral couplings are considered. Further, the additional balance between protein–protein and protein–water interactions has been optimized via multiple ways to reproduce the global extendedness of polypeptide chains, especially for unfolded or disordered proteins. This review aims to summarize the most valuable experience and lessons gained from the past, which, we hope, can facilitate further improvements of both classical FFs and more sophisticated models such as polarizable FFs.

更新日期：2021-10-05

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