Abstract
Computational drug discovery provides an efficient tool for helping large-scale lead molecule screening. One of the major tasks of lead discovery is identifying molecules with promising binding affinities toward a target, a protein in general. The accuracies of current scoring functions that are used to predict the binding affinity are not satisfactory enough. Thus, machine learning or deep learning based methods have been developed recently to improve the scoring functions. In this study, a deep convolutional neural network model (called OnionNet) is introduced; its features are based on rotation-free element-pair-specific contacts between ligands and protein atoms, and the contacts are further grouped into different distance ranges to cover both the local and nonlocal interaction information between the ligand and the protein. The prediction power of the model is evaluated and compared with other scoring functions using the comparative assessment of scoring functions (CASF-2013) benchmark and the v2016 core set of the PDBbind database. The robustness of the model is further explored by predicting the binding affinities of the complexes generated from docking simulations instead of experimentally determined PDB structures.