BindFlow: A Free, User-Friendly Pipeline for Absolute Binding Free Energy Calculations Using Free Energy Perturbation or MM(PB/GB)SA
Alejandro Martínez León, Lucas Andersen, Jochen S. Hub
TL;DR
BindFlow is a free, user-friendly software for calculating binding free energies of molecules with high accuracy and lower computational cost.
Contribution
BindFlow introduces an accessible pipeline for ABFE calculations and demonstrates that MM(PB/GB)SA can rival FEP in accuracy at lower cost.
Findings
BindFlow predictions match experimental results as well as gold-standard methods.
MM(PB/GB)SA achieves correlations comparable to FEP for some systems and force fields.
BindFlow was validated on 139 receptor–ligand pairs across diverse targets.
Abstract
We present BindFlow, a Python-based software for automated absolute binding free energy (ABFE) calculations at the free energy perturbation (FEP) or at the molecular mechanics Poisson–Boltzmann/generalized Born surface area [MM(PB/GB)SA] level of theory. BindFlow is free, open-source, user-friendly, and easily customizable, runs on workstations or distributed computing platforms, and provides extensive documentation and tutorials. BindFlow uses GROMACS as a molecular dynamics engine and provides built-in support for the small-molecule force fields GAFF, OpenFF, and Espaloma, as well as support for user-provided custom force fields. We test BindFlow by computing affinities for 139 receptor–ligand pairs, involving eight different targets, including six soluble proteins, one membrane protein, and one nonprotein host–guest system. We find that the agreement of BindFlow predictions with…
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Taxonomy
TopicsProtein Structure and Dynamics · Receptor Mechanisms and Signaling · Computational Drug Discovery Methods