优先次序
生物信息学
排名(信息检索)
计算机科学
对接(动物)
分子动力学
计算生物学
化学
机器学习
数据挖掘
计算化学
工程类
生物
管理科学
生物化学
医学
基因
护理部
作者
Marko Breznik,Yunhui Ge,Joseph P. Bluck,Hans Briem,David F. Hahn,Clara D. Christ,Jérémie Mortier,David L. Mobley,Katharina Meier
出处
期刊:ChemMedChem
[Wiley]
日期:2022-10-14
卷期号:18 (1)
被引量:3
标识
DOI:10.1002/cmdc.202200425
摘要
Prioritizing molecules for synthesis is a key role of computational methods within medicinal chemistry. Multiple tools exist for ranking molecules, from the cheap and popular molecular docking methods to more computationally expensive molecular-dynamics (MD)-based methods. It is often questioned whether the accuracy of the more rigorous methods justifies the higher computational cost and associated calculation time. Here, we compared the performance on ranking the binding of small molecules for seven scoring functions from five docking programs, one end-point method (MM/GBSA), and two MD-based free energy methods (PMX, FEP+). We investigated 16 pharmaceutically relevant targets with a total of 423 known binders. The performance of docking methods for ligand ranking was strongly system dependent. We observed that MD-based methods predominantly outperformed docking algorithms and MM/GBSA calculations. Based on our results, we recommend the application of MD-based free energy methods for prioritization of molecules for synthesis in lead optimization, whenever feasible.
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