当前位置: X-MOL 学术RSC Med. Chem. › 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.)
Molecular dynamics: a powerful tool for studying the medicinal chemistry of ion channel modulators
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2021-07-22 , DOI: 10.1039/d1md00140j
Daniel Şterbuleac 1, 2, 3
Affiliation  

Molecular dynamics (MD) simulations allow researchers to investigate the behavior of desired biological targets at ever-decreasing costs with ever-increasing precision. Among the biological macromolecules, ion channels are remarkable transmembrane proteins, capable of performing special biological processes and revealing a complex regulatory matrix, including modulation by small molecules, either endogenous or exogenous. Recently, given the developments in ion channel structure determination and accessibility of bio-computational techniques, MD and related tools are becoming increasingly popular in the intense research area regarding ligand–channel interactions. This review synthesizes and presents the most important fields of MD involvement in investigating channel–molecule interactions, including, but not limited to, deciphering the binding modes of ligands to their ion channel targets and the mechanisms through which chemical compounds exert their effect on channel function. Special attention is devoted to the importance of more elaborate methods, such as free energy calculations, while principles regarding drug design and discovery are highlighted. Several technical aspects involving the creation and simulation of channel–molecule MD systems (ligand parameterization, proper membrane setup, system building, etc.) are also presented.

中文翻译:

分子动力学:研究离子通道调节剂药物化学的有力工具

分子动力学 (MD) 模拟使研究人员能够以不断降低的成本和不断提高的精度来研究所需生物靶标的行为。在生物大分子中,离子通道是引人注目的跨膜蛋白,能够执行特殊的生物过程并揭示复杂的调节基质,包括内源性或外源性小分子的调节。最近,鉴于离子通道结构测定和生物计算技术的可及性的发展,MD和相关工具在配体-通道相互作用的密集研究领域变得越来越流行。这篇综述综合并介绍了MD参与研究通道-分子相互作用的最重要领域,包括但不限于破译配体与其离子通道靶标的结合模式以及化合物对通道功能发挥作用的机制。特别关注更复杂方法的重要性,例如自由能计算,同时强调了药物设计和发现的原则。还介绍了涉及通道分子 MD 系统创建和模拟的几个技术方面(配体参数化、适当的膜设置、系统构建等)。
更新日期:2021-08-02
down
wechat
bug