Alchemical Grid Dock (AlGDock): Binding Free Energy Calculations between Flexible Ligands and Rigid Receptors
| Autor: | David D. L. Minh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Binding free energy
FOS: Physical sciences Ligands 010402 general chemistry 01 natural sciences Article Physics - Chemical Physics DOCK 0103 physical sciences Chemical Physics (physics.chem-ph) Physics 010304 chemical physics Ligand Replica Proteins Biological macromolecule Binding potential Biomolecules (q-bio.BM) General Chemistry Grid 0104 chemical sciences 3. Good health Molecular Docking Simulation Computational Mathematics Quantitative Biology - Biomolecules Chemical physics FOS: Biological sciences Thermodynamics Configuration space Software |
| Zdroj: | J Comput Chem |
| ISSN: | 1096-987X 0192-8651 |
| DOI: | 10.1002/jcc.26036 |
| Popis: | Alchemical Grid Dock (AlGDock) is open-source software designed to compute the binding potential of mean force (BPMF) - 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 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. 53 pages, 12 figures, 4 supplemental figures |
| Databáze: | OpenAIRE |
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