DeepDrug3D: Classification of ligand-binding pockets in proteins with a convolutional neural network

摘要

Author summary Small organic ligands bind to the locations of chemical specificity and affinity on their protein targets, called binding sites. A typical ligand-binding site is a small pocket formed by a few residues while the remaining protein structure acts as a framework providing the correct orientation of binding residues. Annotating ligand-binding sites is complicated by a fact that the same small molecule often binds to similar pockets but located in different proteins. In order to improve the detection and classification of binding pockets in proteins, we developed a new computational tool, DeepDrug3D. Our algorithm employs a convolutional neural network, a class of deep learning already commonly used in visual imagery analysis, recommender systems, and natural language processing. DeepDrug3D is able to accurately classify binding sites by learning the patterns of specific molecular interactions between ligands and their protein targets, such as hydrogen bonds, aromatic and hydrophobic contacts. Although the current proof-of-concept implementation is limited to a few most abundant functional classes, the repertoire of pocket types handled by DeepDrug3D will significantly be expanded in the near future.