论文标题
药物结合动力学的分子模拟方法的最新进展
Recent progress in molecular simulation methods for drug binding kinetics
论文作者
论文摘要
由于药物 - 靶标结合动力学对药物疗效的贡献，因此对开发预测药物靶向结合动力学参数的方法具有很高的兴趣。在审查期间，已经开发出广泛的增强采样分子动力学模拟方法来计算药物 - 目标结合动力学并研究结合和关联机制。在这里，我们评估了考虑两个基准系统详细介绍的这些方法的性能：突变体T4溶菌酶配体配合物和一大批N-HSP90抑制剂复合物。结果表明，某些仿真方法已经可以在药物发现或铅优化程序中有效地应用，但是对于更高质量的实验基准数据集进行了进一步的研究以改进和验证计算方法。
Due to the contribution of drug-target binding kinetics to drug efficacy, there is a high level of interest in developing methods to predict drug-target binding kinetic parameters. During the review period, a wide range of enhanced sampling molecular dynamics simulation-based methods has been developed for computing drug-target binding kinetics and studying binding and unbinding mechanisms. Here, we assess the performance of these methods considering two benchmark systems in detail: mutant T4 lysozyme-ligand complexes and a large set of N-HSP90-inhibitor complexes. The results indicate that some of the simulation methods can already be usefully applied in drug discovery or lead optimization programs but that further studies on more high-quality experimental benchmark datasets are necessary to improve and validate computational methods.
