Refining Docking Poses with MM/GBSA

All docking poses were rescored with the MM/GBSA approach, as implemented in the Prime program in the Schrödinger software suite [32 , 41 ]. It employed a single minimised protein–ligand structure, thus establishing an efficient approach to rapidly refine and rescore docking results. We employed the variable dielectric solvent model VSGB 2.0 [52 (link)], which includes empirical corrections for modelling directionality of hydrogen-bond and π-stacking interactions. This approach has been shown to give good binding free energies for a wide range of protein–ligand complexes [53 (link)]. Residues within 5.0 Å of the ligand were allowed to relax during the MM minimisation of the complex, keeping the rest of the structure fixed.