Intrinsically disordered protein‐specific force field CHARMM36IDPSFF,Chemical Biology & Drug Design

当前位置： X-MOL 学术 › Chem. Bio. Drug Des. › 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.)

Intrinsically disordered protein‐specific force field CHARMM36IDPSFF
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2018-07-01 , DOI: 10.1111/cbdd.13342
Hao Liu ₁ , Dong Song ₁ , Hui Lu ₁ , Ray Luo ₂ , Hai-Feng Chen _{1,

3}

Affiliation

Intrinsically disordered proteins (IDPs) are closely related to various human diseases. Because IDPs lack certain tertiary structure, it is difficult to use X‐ray and NMR methods to measure their structures. Therefore, molecular dynamics simulation is a useful tool to study the conformer distribution of IDPs. However, most generic protein force fields were found to be insufficient in simulations of IDPs. Here, we report our development for the CHARMM community. Our residue‐specific IDP force field (CHARMM36IDPSFF) was developed based on the base generic force field with CMAP corrections for all 20 naturally occurring amino acids. Multiple tests show that the simulated chemical shifts with the newly developed force field are in quantitative agreement with NMR experiment and are more accurate than the base generic force field. Comparison of J‐couplings with previous work shows that CHARMM36IDPSFF and its corresponding base generic force field have their own advantages. In addition, CHARMM36IDPSFF simulations also agree with experiment for SAXS profiles and radii of gyration of IDPs. Detailed analysis shows that CHARMM36IDPSFF can sample more diverse and disordered conformers. These findings confirm that the newly developed force field can improve the balance of accuracy and efficiency for the conformer sampling of IDPs.

中文翻译：

固有紊乱的蛋白质特异性力场CHARMM36IDPSFF

内在失调的蛋白质（IDP）与各种人类疾病密切相关。由于IDP缺乏某些三级结构，因此很难使用X射线和NMR方法测量其结构。因此，分子动力学模拟是研究IDP构象异构体分布的有用工具。但是，发现大多数通用蛋白质力场在IDP的模拟中是不够的。在这里，我们报告CHARMM社区的发展。我们的残基特异性IDP力场（CHARMM36IDPSFF）是基于基本通用力场并针对所有20种天然氨基酸进行CMAP校正而开发的。多项测试表明，利用新开发的力场模拟的化学位移与NMR实验定量吻合，并且比基本通用力场更准确。J联轴器与以前的工作比较表明，CHARMM36IDPSFF及其相应的基本通用力场具有自己的优势。此外，CHARMM36IDPSFF模拟也与SAXS剖面和IDP回转半径的实验相吻合。详细的分析表明，CHARMM36IDPSFF可以对更加多样化和无序的构象体进行采样。这些发现证实，新开发的力场可以改善IDP随形取样的准确性和效率之间的平衡。

更新日期：2018-07-01

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11