Department of Chemistry, Illinois Institute of Technology, Chicago, Illinois, 60616.
J Comput Chem. 2020 Mar 15;41(7):715-730. doi: 10.1002/jcc.26036. Epub 2019 Aug 9.
Alchemical Grid Dock (AlGDock) is open-source software designed to compute the binding potential of mean force-the binding free energy between a flexible ligand and a rigid receptor-for a small organic ligand and a biological macromolecule. Multiple BPMFs can be used to rigorously compute binding affinities between flexible partners. AlGDock uses replica exchange between thermodynamic states at different temperatures and receptor-ligand interaction strengths. Receptor-ligand interaction energies are represented by interpolating precomputed grids. Thermodynamic states are adaptively initialized and adjusted on-the-fly to maintain adequate replica exchange rates. In demonstrative calculations, when the bound ligand is treated as fully solvated, AlGDock estimates BPMFs with a precision within 4 kT in 65% and within 8 kT for 91% of systems. It correctly identifies the native binding pose in 83% of simulations. Performance is sometimes limited by subtle differences in the important configuration space of sampled and targeted thermodynamic states. © 2019 Wiley Periodicals, Inc.
炼金网格对接码头 (AlGDock) 是一款开源软件，旨在计算柔性配体与刚性受体之间结合势的平均值 - 小有机配体与生物大分子之间的结合自由能。多个 BPMF 可用于严格计算灵活伙伴之间的结合亲和力。AlGDock 使用不同温度和受体-配体相互作用强度下热力学状态之间的 replica 交换。受体-配体相互作用能量由内插预先计算的网格表示。热力学状态自适应初始化并实时调整以保持足够的 replica 交换率。在示范计算中，当结合配体被视为完全溶剂化时，AlGDock 在 65%的系统中以 4 kT 的精度估计 BPMF，在 91%的系统中以 8 kT 的精度估计 BPMF。它在 83%的模拟中正确识别了天然结合构象。性能有时受到采样和目标热力学状态重要配置空间中细微差异的限制。© 2019 Wiley Periodicals, Inc.
