Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
Biophys J. 2019 Jun 4;116(11):2062-2072. doi: 10.1016/j.bpj.2019.04.017. Epub 2019 Apr 22.
Given by χ torsional angles, rotamers describe the side-chain conformations of amino acid residues in a protein based on the rotational isomers (hence the word rotamer). Constructed rotamer libraries, based on either protein crystal structures or dynamics studies, are the tools for classifying rotamers (torsional angles) in a way that reflect their frequency in nature. Rotamer libraries are routinely used in structure modeling and evaluation. In this perspective article, we would like to encourage researchers to apply rotamer analyses beyond their traditional use. Molecular dynamics (MD) of proteins highlight the in silico behavior of molecules in solution and thus can identify favorable side-chain conformations. In this article, we used simple computational tools to study rotamer dynamics (RD) in MD simulations. First, we isolated each frame in the MD trajectories in separate Protein Data Bank files via the cpptraj module in AMBER. Then, we extracted torsional angles via the Bio3D module in R language. The classification of torsional angles was also done in R according to the penultimate rotamer library. RD analysis is useful for various applications such as protein folding, study of rotamer-rotamer relationship in protein-protein interaction, real-time correlation between secondary structures and rotamers, study of flexibility of side chains in binding site for molecular docking preparations, use of RD as guide in functional analysis and study of structural changes caused by mutations, providing parameters for improving coarse-grained MD accuracy and speed, and many others. Major challenges facing RD to emerge as a new scientific field involve the validation of results via easy, inexpensive wet-lab methods. This realm is yet to be explored.
给定 χ 扭转角，构象异构体描述了蛋白质中氨基酸残基的侧链构象，基于旋转异构体（因此称为构象异构体）。基于蛋白质晶体结构或动力学研究构建的构象异构体库是对构象异构体（扭转角）进行分类的工具，反映了它们在自然界中的频率。构象异构体库常用于结构建模和评估。在这篇观点文章中，我们希望鼓励研究人员超越传统用途应用构象分析。蛋白质的分子动力学（MD）突出了分子在溶液中的计算行为，因此可以识别有利的侧链构象。在本文中，我们使用简单的计算工具来研究 MD 模拟中的构象动力学（RD）。首先，我们通过 AMBER 中的 cpptraj 模块将 MD 轨迹中的每个帧分离到单独的蛋白质数据库文件中。然后，我们通过 R 语言中的 Bio3D 模块提取扭转角。扭转角的分类也根据倒数第二个构象异构体库在 R 中进行。RD 分析可用于各种应用，例如蛋白质折叠、研究蛋白质-蛋白质相互作用中的构象异构体-构象异构体关系、二级结构和构象异构体之间的实时相关性、结合位点侧链灵活性的研究用于分子对接准备、将 RD 用作功能分析和研究突变引起的结构变化的指南、为改进粗粒度 MD 的准确性和速度提供参数，以及其他许多应用。RD 作为一个新的科学领域出现所面临的主要挑战涉及通过简单、廉价的湿实验室方法验证结果。这一领域尚未得到探索。
