ViTScore: A Novel Three-Dimensional Vision Transformer Method for Accurate Prediction of Protein–Ligand Docking Poses

Protein-ligand interactions (PLIs) are essential for cellular activities and drug discovery, and due to the complexity and high cost of experimental methods, there is a great demand for computational approaches, such as protein-ligand docking, to decipher PLI patterns. One of the most challenging aspects of protein-ligand docking is to identify near-native conformations from a set of poses, but traditional scoring functions still have limited accuracy. Therefore, new scoring methods are urgently needed for methodological and/or practical implications. We present a novel deep learning-based scoring function for ranking protein-ligand docking poses based on Vision Transformer (ViT), named ViTScore. To recognize near-native poses from a set of poses, ViTScore voxelizes the protein-ligand interactional pocket into a 3D grid labeled by the occupancy contribution of atoms in different physicochemical classes. This allows ViTScore to capture the subtle differences between spatially and energetically favorable near-native poses and unfavorable non-native poses without needing extra information. After that, ViTScore will output the prediction of the root mean square deviation (rmsd) of a docking pose with reference to the native binding pose. ViTScore 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. Moreover, the results demonstrate that ViTScore is a promising scoring function for protein-ligand docking, and it can be used to accurately identify near-native poses from a set of poses. Furthermore, the results suggest that ViTScore is a powerful tool for protein-ligand docking, and it can be used to accurately identify near-native poses from a set of poses. Additionally, ViTScore can be used to identify potential drug targets and to design new drugs with improved efficacy and safety.