# BindFlow: A Free, User-Friendly Pipeline for Absolute Binding Free Energy Calculations Using Free Energy Perturbation or MM(PB/GB)SA

## 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.

## Key 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 experiments
is overall similar to gold standards in the field. Interestingly,
we find that MM­(PB/GB)­SA achieves correlations that, for some systems
and force fields, approach those obtained with FEP while requiring
only a fraction of the computational cost. This study establishes
BindFlow as a validated and accessible tool for ABFE calculations.