Free energy perturbation calculations of tetrahydroquinolines complexed to the first bromodomain of BRD4

Alchemical free energy perturbation (FEP) theory is widely used nowadays to calculate protein–ligand binding energies, often in support of drug discovery endeavours. We assess the accuracy and sensitivity absolute FEP energies with respect CHARMM/CGenFF AMBER/GAFF force field parameterisations for a set tetrahydroquinoline inhibitors first bromodomain BRD4, target keen interest development anti-cancer drugs. find that better able than cover range distinguish between relative 16 ligands.