Refinement of the Sugar–Phosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B-DNA,Journal of Chemical Theory and Computation

当前位置： X-MOL 学术 › J. Chem. Theory Comput. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Refinement of the Sugar–Phosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B-DNA
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2015-11-20 00:00:00 , DOI: 10.1021/acs.jctc.5b00716
Marie Zgarbová ₁ , Jiří Šponer _{1,

2} , Michal Otyepka ₁ , Thomas E. Cheatham ₃ , Rodrigo Galindo-Murillo ₃ , Petr Jurečka ₁

Affiliation

Z-DNA duplexes are a particularly complicated test case for current force fields. We performed a set of explicit solvent molecular dynamics (MD) simulations with various AMBER force field parametrizations including our recent refinements of the ε/ζ and glycosidic torsions. None of these force fields described the ZI/ZII and other backbone substates correctly, and all of them underpredicted the population of the important ZI substate. We show that this underprediction can be attributed to an inaccurate potential for the sugar–phosphate backbone torsion angle β. We suggest a refinement of this potential, β_OL1, which was derived using our recently introduced methodology that includes conformation-dependent solvation effects. The new potential significantly increases the stability of the dominant ZI backbone substate and improves the overall description of the Z-DNA backbone. It also has a positive (albeit small) impact on another important DNA form, the antiparallel guanine quadruplex (G-DNA), and improves the description of the canonical B-DNA backbone by increasing the population of BII backbone substates, providing a better agreement with experiment. We recommend using β_OL1 in combination with our previously introduced corrections, εζ_OL1 and χ_OL4, (the combination being named OL15) as a possible alternative to the current β torsion potential for more accurate modeling of nucleic acids.

中文翻译：

细化AMBER力场的糖-磷酸盐骨干扭转Beta改善了Z-DNA和B-DNA的描述

Z-DNA双链体是用于当前力场的特别复杂的测试案例。我们使用各种AMBER力场参数化进行了一组显式的溶剂分子动力学（MD）模拟，包括我们最近对ε/ζ和糖苷扭转的改进。这些力场中没有一个能正确描述ZI / ZII和其他主干亚状态，并且所有这些都低估了重要ZI亚州的人口。我们表明，这种低估可以归因于糖-磷酸盐主链扭转角β的潜在误差。我们建议对此潜能进行细化，_βOL1，它是使用我们最近引入的方法得出的，该方法包括与构象有关的溶剂化效应。新的潜力大大增加了主要ZI骨架亚状态的稳定性，并改善了Z-DNA骨架的整体描述。它还对另一种重要的DNA形式，即反平行鸟嘌呤四联体（G-DNA）具有积极（尽管很小）的影响，并通过增加BII骨架亚基的数量来改善对规范B-DNA骨架的描述，从而提供了更好的协议与实验。我们建议使用β _OL1结合我们前面介绍的修正，εζ _OL1和χ _OL4（组合称为OL15）作为当前β扭转潜力的一种可能替代方案，用于更精确的核酸建模。

更新日期：2015-11-20

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南