Department of Chemistry, Illinois Institute of Technology, Chicago, Illinois, 60616.
Departments of Chemistry and Physics, University of Illinois at Chicago, Chicago, Illinois, 60607.
J Comput Chem. 2018 Apr 30;39(11):621-636. doi: 10.1002/jcc.25139. Epub 2017 Dec 22.
According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations from the unbound ensemble are discretely translated across rigid receptor conformations. Results for standard binding free energies between T4 lysozyme and 141 small organic molecules are in good agreement with previous alchemical calculations based on (1) a flexible complex ( R≈0.9 for 24 systems) and (2) flexible ligand with multiple rigid receptor configurations ( R≈0.8 for 141 systems). While the FFT is routinely used for molecular docking, to our knowledge this is the first time that the algorithm has been used for rigorous binding free energy calculations. © 2017 Wiley Periodicals, Inc.
根据隐配体理论，标准结合自由能是平均结合势（BPMF）的指数平均值，平均结合势是未结合配体系综与刚性受体之间相互作用能的指数平均值。在这里，我们使用快速傅里叶变换（FFT）通过计算未结合系综中刚性配体构象离散平移穿过刚性受体构象时的相互作用能，有效地评估 BPMF。T4 溶菌酶与 141 个小分子之间标准结合自由能的结果与以前基于（1）柔性复合物（24 个系统中 R≈0.9）和（2）具有多个刚性受体构象的柔性配体（141 个系统中 R≈0.8）的的量子化学计算结果吻合良好。虽然 FFT 通常用于分子对接，但据我们所知，这是该算法首次用于严格的结合自由能计算。 © 2017 年 Wiley 期刊出版公司
