Development of Accurate Force Fields for Mg²⁺ and Triphosphate Interactions in ATP·Mg²⁺ and GTP·Mg²⁺ Complexes.

IF 5.7 1区化学 Q2 CHEMISTRY, PHYSICAL Journal of Chemical Theory and Computation Pub Date : 2024-11-21 DOI:10.1021/acs.jctc.4c01142

Fangchen Hu, Yuwei Zhang, Pengfei Li, Ruibo Wu, Fei Xia

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引用次数: 0

Abstract

In cells, adenosine triphosphate (ATP) and guanosine triphosphate (GTP) molecules typically form tricoordinated or bicoordinated ATP·Mg²⁺ or GTP·Mg²⁺ complexes with Mg²⁺ ions and bind to proteins, participating in and regulating many important cellular functions. The accuracy of their force field parameters plays a crucial role in studying the function-related conformations of ATP·Mg²⁺ or GTP·Mg²⁺ using molecular dynamics (MD) simulations. The parameters developed based on the methyl triphosphate model in existing AMBER force fields cannot accurately describe the conformational distribution of tricoordinated or bicoordinated ATP·Mg²⁺ or GTP·Mg²⁺ complexes in solution. In this study, we develop force field parameters for the triphosphate group based on the new ribosyl triphosphate model, considering the dihedral coupling effect, accurate van der Waals (vdW) interactions, and the influence of strongly polarized charges on conformational balance. The new force fields can accurately describe the conformational balance of tricoordinated and bicoordinated ATP·Mg²⁺ or GTP·Mg²⁺ conformations in solution and can be applied to simulate biological systems containing ATP·Mg²⁺ or GTP·Mg²⁺ complexes.

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开发 ATP-Mg2+ 和 GTP-Mg2+ 复合物中 Mg2+ 和三磷酸相互作用的精确力场。

在细胞中，三磷酸腺苷（ATP）和三磷酸鸟苷（GTP）分子通常与 Mg2+ 离子形成三配位或双配位 ATP-Mg2+ 或 GTP-Mg2+ 复合物，并与蛋白质结合，参与和调控许多重要的细胞功能。在利用分子动力学（MD）模拟研究 ATP-Mg2+ 或 GTP-Mg2+ 与功能相关的构象时，其力场参数的准确性起着至关重要的作用。现有 AMBER 力场中基于三磷酸甲酯模型开发的参数无法准确描述三配位或双配位 ATP-Mg2+ 或 GTP-Mg2+ 复合物在溶液中的构象分布。在本研究中，我们基于新的核糖基三磷酸模型开发了三磷酸基团的力场参数，考虑了二面耦合效应、精确的范德华（vdW）相互作用以及强极化电荷对构象平衡的影响。新力场能准确描述三配位和双配位 ATP-Mg2+ 或 GTP-Mg2+ 在溶液中的构象平衡，可用于模拟含有 ATP-Mg2+ 或 GTP-Mg2+ 复合物的生物系统。

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.