This repository contains the input files for the studies 'L-ABF-OPES: Absolute Binding Free Energy Calculations Using Local Adaptively Biased Force and On-the-Fly Probability Enhanced Sampling' (https://doi.org/10.48550/arXiv.2502.17233) and 'From Water Networks to Binding Affinities: Resolving Solvation Dynamics for Accurate Protein-Ligand Predictions' (https://doi.org/10.1101/2025.10.17.683050).

About

L-ABF-OPES is a computational method designed to calculate absolute binding free energy (ABFE). The inputs provided here were used to evaluate the ABFE of:

• The BRD4 complex with 11 different drug-like molecules
• The Benzimidazole-Trypsin system
• 5I1Q (TAF1(2) in complex with [6-(but-3-en-1-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl]-N,N-dimethylbenzamide), 1I05 (MUP-I in complex with 6-hydroxy-6-methyl-3-heptanone), 5I40 (Bromo-domain containing protein in complex with 6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one), 2XAB (Heat shock protein HSP90-$\alpha$ in complex with (1,3-dihydro-isoindol-2-yl)-(2,4-dihydroxy-5-isopropyl-phenyl)-methanone), and 2XJG (Heat shock protein HSP90-$\alpha$ in complex with (1,3-dihydro-isoindol-2-yl)-(2-hydroxy-5-isopropyl-4-methoxy-phenyl)-methanone)

Repository Contents

This repository includes all the neccesary inputs to run L-ABF-OPES uisng Tinker-HP/Colvars:

• Electrostatic (ELE) and van der Waals (VDW) inputs for complex and solvent phases.
• Restraint-free gas phase simulation to calculate the DBC restraint correction