New tricks for old dogs: improving the accuracy of biomolecular force fields by pair-specific corrections to non-bonded interactions.
New tricks for old dogs: improving the accuracy of biomolecular force fields by pair-specific corrections to non-bonded interactions.
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DOI：
10.1039/c7cp08185e
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发表时间：
2018-03-28
期刊：
影响因子：
--
通讯作者：
Aksimentiev A
中科院分区：
文献类型：
--
作者：
Yoo J;Aksimentiev A
与普通聚合物不同，绝大多数生物大分子采用定义其功能的高度有序的三维结构。将生物聚合物折叠成独特的三维结构或将几个生物聚合物组装成一个功能单元的关键是吸引力和排斥力之间的微妙平衡，这也使这种自组装在生理条件下是可逆的。全原子分子动力学(MD)方法已经成为研究单个生物分子及其功能组装的有力工具，包括日益复杂的系统。然而，并行计算技术的进步已经超过了基本理论模型--分子力场的发展，将MD方法推向了未经测试的领域。最近对MD方法的测试发现，最常用的分子力场是不平衡的，高估了带电基团和疏水基团之间的吸引力相互作用，这可能会促进多组分蛋白质、核酸和脂类体系的MD模拟中的人工聚集。改善力场的一种方法是通过NBFIX修正方法，在这种方法中，通过对非键相互作用进行原子对特定的调整，根据实验测量的量(如渗透压)来校准分子间力。在这篇文章中，我们回顾了对Amber和CHARMM力场的NBFIX修正的进展，并讨论了它们在电解质溶液、密集DNA系统、Holliday连接、蛋白质折叠和脂质双层膜的MD模拟中的意义。
In contrast to ordinary polymers, the vast majority of biological macromolecules adopt highly ordered three-dimensional structures that define their functions. The key to folding of a biopolymer into a unique 3D structure or to assembly of several biopolymers into a functional unit is a delicate balance between the attractive and repulsive forces that also makes such self-assembly reversible under physiological conditions. The all-atom molecular dynamics (MD) method has emerged as a powerful tool for studies of individual biomolecules and their functional assemblies, encompassing systems of ever increasing complexity. However, advances in parallel computing technology have outpaced development of the underlying theoretical models—the molecular force fields, pushing the MD method into untested territory. Recent tests of the MD method have found the most commonly used molecular force fields to be out of balance, overestimating attractive interactions between charged and hydrophobic groups, which can promote artificial aggregation in MD simulations of multi-component protein, nucleic acid, and lipid systems. One route to improving the force fields is through the NBFIX corrections method, in which the intermolecular forces are calibrated against experimentally measured quantities such as osmotic pressure by making atom pair-specific adjustments to the non-bonded interactions. In this article, we review development of the NBFIX corrections to the AMBER and CHARMM force fields and discuss their implications for MD simulations of electrolyte solutions, dense DNA systems, Holliday junctions, protein folding and lipid bilayer membranes.