School of Science, Shandong Jiaotong University, Jinan-250357, China.
Mini Rev Med Chem. 2024;24(14):1323-1333. doi: 10.2174/0113895575252165231122095555.
Rational predictions on binding kinetics parameters of drugs to targets play significant roles in future drug designs. Full conformational samplings of targets are requisite for accurate predictions of binding kinetic parameters. In this review, we mainly focus on the applications of enhanced sampling technologies in calculations of binding kinetics parameters and residence time of drugs. The methods involved in molecular dynamics simulations are applied to not only probe conformational changes of targets but also reveal calculations of residence time that is significant for drug efficiency. For this review, special attention are paid to accelerated molecular dynamics (aMD) and Gaussian aMD (GaMD) simulations that have been adopted to predict the association or disassociation rate constant. We also expect that this review can provide useful information for future drug design.
理性预测药物与靶点的结合动力学参数在未来的药物设计中起着重要作用。为了准确预测结合动力学参数，需要对靶点进行全构象采样。在这篇综述中，我们主要关注增强采样技术在药物结合动力学参数和药物滞留时间计算中的应用。所涉及的分子动力学模拟方法不仅可用于探测靶点的构象变化，还可揭示对药物效率有重要意义的滞留时间的计算。对于本篇综述，我们特别关注已被用于预测结合或离解速率常数的加速分子动力学（aMD）和高斯加速分子动力学（GaMD）模拟。我们还期望这篇综述能为未来的药物设计提供有用的信息。
