BAT2: an Open-Source Tool for Flexible, Automated, and Low Cost Absolute Binding Free Energy Calculations.
Germano HeinzelmannDavid J HugginsMichael K GilsonPublished in: Journal of chemical theory and computation (2024)
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, support 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.
Keyphrases
- molecular dynamics
- density functional theory
- drug discovery
- low cost
- binding protein
- dna binding
- monte carlo
- deep learning
- virtual reality
- high throughput
- transcription factor
- climate change
- protein protein
- molecular dynamics simulations
- molecularly imprinted
- small molecule
- high resolution
- tandem mass spectrometry
- solid phase extraction