BA-Pred and RMSD-Pred: Integrated Graph Neural Network Models for Accurate Protein–Ligand Binding Affinity and Binding Pose Prediction

, while RMSD-Pred exhibited strong docking power with a top-1 success rate of 96%, comparable to the best reported deep-learning scoring functions. The robust generalization capability of RMSD-Pred was further validated on the external Astex diverse set and PoseBusters benchmarks, where it significantly improved the pose selection success rates of AutoDock-GPU by up to 33.1%. The accuracy of our methodology was demonstrated on pharmaceutical targets in the 16th Critical Assessment of Structure Prediction, where our approach ranked second in the ligand binding affinity prediction category. By using our models, an integrated pipeline was developed for virtual screening, where pose selection was performed with RMSD-Pred and binding affinities were predicted with BA-Pred. This combined approach demonstrated robust screening performance, achieving an enrichment factor (EF) 1% of 21.1 on the CASF-2016 benchmark. Furthermore, on the LIT-PCBA benchmark, rescoring poses docked by AutoDock-GPU with our pipeline significantly improved the EF 1% from 2.18 to 3.19. These various benchmark results demonstrate that our graph-neural network models show good and balanced performance in diverse protein-ligand interaction prediction tasks. Thus, we expect that our models will serve as a promising framework to accelerate the drug discovery process.