AA-Score: a New Scoring Function Based on Amino Acid-Specific Interaction for Molecular Docking

The protein–ligand scoring function plays an important role in computer-aided drug discovery and is heavily used in virtual screening and lead optimization. In this study, we developed a new empirical protein–ligand scoring function with amino acid-specific interaction components for hydrogen bond, van der Waals, and electrostatic interactions. In addition, hydrophobic, π-stacking, π-cation, and metal–ligand interactions are also included in the new scoring function. To better evaluate the performance of the AA-Score, we generated several new test sets for evaluation of scoring, ranking, and docking performances, respectively. Extensive tests show that AA-Score performs well on scoring, docking, and ranking as compared to other widely used traditional scoring functions. The performance improvement of AA-Score benefits from the decomposition of individual interaction into amino acid-specific types. To facilitate applications, we developed an easy-to-use tool to analyze protein–ligand interaction fingerprint and predict binding affinity using the AA-Score. The source code and associated running examples can be found at https://github.com/xundrug/AA-Score-Tool.