Binding Energy Estimation
Lead Finder is capable of predicting free energy of protein-ligand binding with high accuracy. This functionality is novel to docking software since binding energy calculation is usually done in separate software packages that are based on various theoretical approaches including free energy perturbation, linear interaction energy, etc. Such packages require high level of expertise and involvement in specific fields of computational chemistry and are often expensive and time-consuming to implement.
Lead Finder performs high-accuracy calculation of the free energy of binding at the same time when a ligand docking computation is done. A separate scoring function, called dG-score function, is used to calculate binding energy of protein-ligand interaction. The accuracy of binding energy prediction with Lead Finder has been validated on a set of 330 experimentally characterized protein-ligand complexes with a broad distribution of ligand binding affinities and other physicochemical properties (see the
section for more details). On this test set, Lead Finder has achieved an RMSD of 1.5 kcal/mol (deviation from the experimentally obtained values).
Binding energy calculations can be performed either concurrently with ligand docking or separately for a predetermined protein-ligand structure, obtained from experimental data or other molecular modeling studies. The ability of Lead Finder to accurately predict free energy of ligand binding can be extremely valuable in drug discovery studies, modeling ADMET properties in silico, studies of enzyme specificity and rational enzyme design.