The fine art of preparing membrane transport proteins for biomolecular simulations: Concepts and practical considerations.
The fine art of preparing membrane transport proteins for biomolecular simulations: Concepts and practical considerations.
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DOI：
10.1016/j.ymeth.2020.02.009
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发表时间：
2021-01
期刊：
影响因子：
4.8
通讯作者：
Sahai, Michelle A.
中科院分区：
文献类型：
--
作者：
Shiref, Hana;Bergman, Shana;Clivio, Sophie;Sahai, Michelle A.
关键词：
分子动力学 (MD) 模拟已发展成为双分子研究中的宝贵工具，因为该方法能够捕获描述生物分子系统功能和理化性质的分子事件和结构转变。由于更高效算法的逐步发展、可用计算资源的扩展以及更先进方法的出现，计算研究的范围随着时间的推移而大大增加。由于新型精神活性物质（NPS）的出现，我们现在可以访问大量在线数据库、软件包、更大的分子系统和新型配体。鉴于该领域取得了如此多的进步，毫无疑问，新手在运行第一次 MD 模拟之前就会发现建立蛋白质-配体系统具有挑战性。这些初始步骤，如同源建模、配体对接、参数化、蛋白质制备和膜设置，已成为药物发现流程的基本组成部分，生物分子科学的许多领域都受益于这些技术提供的应用。然而，它们的使用仍然没有标准。因此，我们本次综述的目的是对需要考虑的各种概念和方法提供清晰的概述，为膜转运蛋白（与不同兴奋剂复合的全长人类多巴胺转运蛋白（hDAT））的案例研究提供工作流程，其中 MD 模拟最近已成功应用。
Molecular dynamics (MD) simulations have developed into an invaluable tool in bimolecular research, due to the capability of the method in capturing molecular events and structural transitions that describe the function as well as the physiochemical properties of biomolecular systems. Due to the progressive development of more efficient algorithms, expansion of the available computational resources, as well as the emergence of more advanced methodologies, the scope of computational studies has increased vastly over time. We now have access to a multitude of online databases, software packages, larger molecular systems and novel ligands due to the phenomenon of emerging novel psychoactive substances (NPS). With so many advances in the field, it is understandable that novices will no doubt find it challenging setting up a protein-ligand system even before they run their first MD simulation. These initial steps, such as homology modelling, ligand docking, parameterization, protein preparation and membrane setup have become a fundamental part of the drug discovery pipeline, and many areas of biomolecular sciences benefit from the applications provided by these technologies. However, there still remains no standard on their usage. Therefore, our aim within this review is to provide a clear overview of a variety of concepts and methodologies to consider, providing a workflow for a case study of a membrane transport protein, the full-length human dopamine transporter (hDAT) in complex with different stimulants, where MD simulations have recently been applied successfully.
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影响因子：
14.9
作者：
wwPDB consortium
通讯作者：
wwPDB consortium
DOI：
10.1107/s0907444913007051
发表时间：
2013-05
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Biasini M;Schmidt T;Bienert S;Mariani V;Studer G;Haas J;Johner N;Schenk AD;Philippsen A;Schwede T
通讯作者：
Schwede T
影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
影响因子：
4.7
作者：
Bisgaard, Heidi;Larsen, M. Andreas B.;Mazier, Sonia;Beuming, Thijs;Newman, Amy Hauck;Weinstein, Hare;Shi, Lei;Loland, Claus J.;Gether, Ulrik
通讯作者：
Gether, Ulrik
影响因子：
16.8
作者：
Coleman JA;Gouaux E
通讯作者：
Gouaux E