School of Biotechnology, International University , Vietnam National University , Ho Chi Minh City 700000 , Vietnam.
Department of Medicine and Division of Hematology and Oncology , Loma Linda University Medical Center , Loma Linda , California 92350 , United States.
J Chem Inf Model. 2018 Aug 27;58(8):1473-1482. doi: 10.1021/acs.jcim.8b00261. Epub 2018 Jul 25.
Conventional de novo drug design is time consuming, laborious, and resource intensive. In recent years, emerging in silico approaches have been proven to be critical to accelerate the process of bringing drugs to market. Molecular dynamics (MD) simulations of single molecule and molecular complexes have been commonly applied to achieve accurate binding modes and binding energies of drug-receptor interactions. A derivative of MD, namely, steered molecular dynamics (SMD), has been demonstrated as a promising tool for rational drug design. In this paper, we review various studies over the last 20 years using SMD simulations, thus paving the way to determine the relationship between protein structure and function. In addition, the paper highlights the use of SMD simulation for in silico drug design. We also aim to establish an understanding on the key interactions which play a crucial role in the stabilization of peptide-ligand interfaces, the binding and unbinding mechanism of the ligand-protein complex, the mechanism of ligand translocating via membrane, and the ranking of different ligands on receptors as therapeutic candidates.
传统的从头药物设计既耗时又费力，且资源密集。近年来，新兴的计算方法已被证明对加速药物上市进程至关重要。单分子和分子复合物的分子动力学（MD）模拟已广泛应用于实现药物-受体相互作用的准确结合模式和结合能。MD 的一个衍生方法，即定向分子动力学（SMD），已被证明是一种很有前途的合理药物设计工具。本文回顾了过去 20 年来使用 SMD 模拟的各种研究，从而为确定蛋白质结构和功能之间的关系铺平了道路。此外，本文还强调了 SMD 模拟在计算机药物设计中的应用。我们还旨在建立对关键相互作用的理解，这些相互作用在肽配体界面的稳定、配体-蛋白复合物的结合和解离机制、配体通过膜转运的机制以及作为治疗候选物的不同配体在受体上的排序中起着至关重要的作用。
