Protein-ligand interactions (PLIs) are essential for cellular activities and drug discovery. But due to the complexity and high cost of experimental methods, there is a great demand for computational approaches to recognize PLI patterns, such as protein-ligand docking. In recent years, more and more models based on machine learning have been developed to directly predict the root mean square deviation (RMSD) of a ligand docking pose with reference to its native binding pose. However, new scoring methods are pressingly needed in methodology for more accurate RMSD prediction. We present a new deep learning-based scoring method for RMSD prediction of protein-ligand docking poses based on a Graphormer method and Shell-like graph architecture, named GSScore. To recognize near-native conformations from a set of poses, GSScore takes atoms as nodes and then establishes the docking interface of protein-ligand into multiple bipartite graphs within different shell ranges. Benefiting from the Graphormer and Shell-like graph architecture, GSScore can effectively capture the subtle differences between energetically favorable near-native conformations and unfavorable non-native poses without extra information. GSScore was extensively evaluated on diverse test sets including a subset of PDBBind version 2019, CASF2016 as well as DUD-E, and obtained significant improvements over existing methods in terms of RMSE, $R$ (Pearson correlation coefficient), Spearman correlation coefficient and Docking power.

Protein-ligand interactions (PLIs) play important roles in cellular activities and drug discovery. Due to the technical difficulty and high cost of experimental methods, there is considerable interest in the development of computational approaches, such as protein-ligand docking, to decipher PLI patterns. One of the most important and difficult aspects of protein-ligand docking is recognizing near-native conformations from a set of decoys, but unfortunately, traditional scoring functions still suffer from limited accuracy. Therefore, new scoring methods are pressingly needed in methodological and/or practical implications. We present a new deep learning-based scoring function for ranking protein-ligand docking models based on Vision Transformer(ViT), named ViTRMSE. To recognize near-native conformations from a set of decoys, ViTRMSE voxelizes the protein-ligand interactional pocket into a 3D grid labeled by the occupancy contribution of atoms in different physicochemical classes. Benefiting from the Vision Transformer architecture, ViTRMSE can effectively capture the subtle differences between spatially and energetically favorable near-native conformations and unfavorable non-native decoys without needing extra information. ViTRMSE is extensively evaluated on diverse test sets including PDBbind2019 and CASF2016, and obtains significant improvements over existing methods in terms of RMSE, R and docking power.

MOTIVATION: Protein-protein interactions (PPI) play important roles in cellular activities. Due to the technical difficulty and high cost of experimental methods, there are considerable interests towards the development of computational approaches, such as protein docking, to decipher PPI patterns. One of the important and difficult aspects in protein docking is recognizing near-native conformations from a set of decoys, but unfortunately, traditional scoring functions still suffer from limited accuracy. Therefore, new scoring methods are pressingly needed in methodological and/or practical implications. RESULTS: We present a new deep learning-based scoring method for ranking protein-protein docking models based on a 3D RepVGG network, named TRScore. To recognize near-native conformations from a set of decoys, TRScore voxelizes the protein-protein interface into a 3D grid labeled by the number of atoms in different physicochemical classes. Benefiting from the deep convolutional RepVGG architecture, TRScore can effectively capture the subtle differences between energetically favorable near-native models and unfavorable non-native decoys without needing extra information. TRScore was extensively evaluated on diverse test sets including protein-protein docking benchmark 5.0 update set, DockGround decoy set, as well as realistic CAPRI decoy set and overall obtained a significant improvement over existing methods in cross-validation and independent evaluations. AVAILABILITY AND IMPLEMENTATION: Codes available at: https://github.com/BioinformaticsCSU/TRScore.