Abstract
The core of large-scale drug virtual screening is to select the binders accurately and efficiently with high affinity from large libraries of small molecules in which non-binders are usually dominant. The binding affinity is significantly influenced by the protein pocket, ligand spatial information, and residue types/atom types. Here, we used the pocket residues or ligand atoms as the nodes and constructed edges with the neighboring information to comprehensively represent the protein pocket or ligand information. Moreover, the model with pre-trained molecular vectors performed better than the one-hot representation. The main advantage of DeepBindGCN is that it is independent of docking conformation, and concisely keeps the spatial information and physical-chemical features. Using TIPE3 and PD-L1 dimer as proof-of-concept examples, we proposed a screening pipeline integrating DeepBindGCN and other methods to identify strong-binding-affinity compounds. It is the first time a non-complex-dependent model has achieved a root mean square error (RMSE) value of 1.4190 and Pearson r value of 0.7584 in the PDBbind v.2016 core set, respectively, thereby showing a comparable prediction power with the state-of-the-art affinity prediction models that rely upon the 3D complex. DeepBindGCN provides a powerful tool to predict the protein-ligand interaction and can be used in many important large-scale virtual screening application scenarios.