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 modeling, 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.

中文翻译：

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为生物分子模拟制备膜转运蛋白的艺术：概念和实际考虑

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物理化学特性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。由于新兴的新型精神活性物质 (NPS) 现象，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。随着该领域的如此多的进步，可以理解的是，新手在运行他们的第一个 MD 模拟之前无疑会发现设置蛋白质-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，已成为药物发现管道的基本部分，生物分子科学的许多领域都受益于这些技术提供的应用。但是，它们的使用仍然没有标准。因此，我们在这篇综述中的目的是清楚地概述要考虑的各种概念和方法，为膜转运蛋白的案例研究提供工作流程，全长人多巴胺转运蛋白 (hDAT) 与不同的复合物兴奋剂，最近成功应用了 MD 模拟。