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, pi-stacking, pi-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.

Automated summary

This study presents a new protein-ligand scoring function called AA-Score, which shows improved performance in scoring, docking, and ranking compared to traditional scoring functions. The function utilizes amino acid-specific interaction components and includes various types of interactions. An easy-to-use tool for analyzing protein-ligand interactions and predicting binding affinity using AA-Score is also developed. The source code and examples can be found at https://github.com/xundrug/AA-Score-Tool.