DeepBindGCN: Integrating Molecular Vector Representation with Graph Convolutional Neural Networks for Accurate Protein-Ligand Interaction Prediction

Abstract

AbstractThe core of large-scale drug virtual screening is to accurately and efficiently select the binders with high affinity from large libraries of small molecules in which nonbinders are usually dominant. The protein pocket, ligand spatial information, and residue types/atom types play a pivotal role in binding affinity. Here we used the pocket residues or ligand atoms as nodes and constructed edges with the neighboring information to comprehensively represent the protein pocket or ligand information. Moreover, we find that the model with pre-trained molecular vectors performs better than the onehot representation. The main advantage of DeepBindGCN is that it is non-dependent on docking conformation and concisely keeps the spatial information and physical-chemical feature. Notably, the DeepBindGCN_BC has high precision in many DUD.E datasets, and DeepBindGCN_RG achieve a very low RMSE value in most DUD.E datasets. Using TIPE3 and PD-L1 dimer as proof-of-concept examples, we proposed a screening pipeline by integrating DeepBindGCN_BC, DeepBindGCN_RG, and other methods to identify strong binding affinity compounds. In addition, a DeepBindGCN_RG_x model has been used for comparing performance with other methods in PDBbind v.2016 and v.2013 core set. It is the first time that a non-complex dependent model achieves an RMSE value of 1.3843 and Pearson-R value of 0.7719 in the PDBbind v.2016 core set, showing comparable prediction power with the state-of-the-art affinity prediction models that rely upon the 3D complex. Our DeepBindGCN provides a powerful tool to predict the protein-ligand interaction and can be used in many important large-scale virtual screening application scenarios.