BAT2: An open-source tool for flexible, automated and low cost absolute binding free energy calculations

20 February 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Absolute binding free energy (ABFE) calculations with all-atom molecular dynamics (MD) have the potential to greatly reduce costs in the first stages of drug discovery. Here we introduce BAT2, the new version of the Binding Affinity Tool (BAT.py), designed to combine full automation of ABFE calculations with high-performance MD simulations, making it a potential tool for virtual screening. We describe and test several changes and new features that were incorporated into the code, such as relative restraints between the protein and the ligand instead of using fixed dummy atoms, sup- port for the OpenMM simulation engine, a merged approach to the application/release of restraints, support for cobinders and proteins with multiple chains, and many others. We also reduced the simulation times for each ABFE calculation, assessing the effect on the expected robustness and accuracy of the calculations.

Keywords

Free energy calculations
Virtual Screening
Molecular dynamics

Supplementary materials

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Description
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Table S1
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Supplementary results for BRD4(2)
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Table S2
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Supplementary results for HIV-1 protease
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Input files
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Input files to reproduce the paper's results.
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