Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.
Curr Opin Struct Biol. 2020 Apr;61:213-221. doi: 10.1016/j.sbi.2020.01.014. Epub 2020 Feb 26.
Simulations can provide detailed insight into the molecular processes involved in drug action, such as protein-ligand binding, and can therefore be a valuable tool for drug design and development. Processes with a large range of length and timescales may be involved, and understanding these different scales typically requires different types of simulation methodology. Ideally, simulations should be able to connect across scales, to analyze and predict how changes at one scale can influence another. Multiscale simulation methods, which combine different levels of treatment, are an emerging frontier with great potential in this area. Here we review multiscale frameworks of various types, and selected applications to biomolecular systems with a focus on drug-ligand binding.
模拟可以深入了解药物作用中涉及的分子过程，如蛋白质-配体结合，因此可以成为药物设计和开发的有价值的工具。可能涉及范围广泛的长度和时间尺度的过程，理解这些不同的尺度通常需要不同类型的模拟方法。理想情况下，模拟应该能够跨尺度连接，分析和预测一个尺度的变化如何影响另一个尺度。多尺度模拟方法，将不同的处理层次结合在一起，是这一领域具有巨大潜力的新兴前沿。在这里，我们回顾了各种类型的多尺度框架，并选择了生物分子系统中药物-配体结合的应用进行了重点介绍。
