Location and properties of ligand binding sites provide important information to uncover protein functions and to direct structure-based drug design approaches. However, as binding site detection depends on the three-dimensional (3D) structural data of proteins, functional analysis based on protein ligand binding sites is formidable for proteins without structural information. Recent developments in protein structure prediction and the 3D structures built by AlphaFold provide an unprecedented opportunity for analyzing ligand binding sites in human proteins. Here, we constructed the CavitySpace database, the first pocket library for all the proteins in the human proteome, using a widely-applied ligand binding site detection program CAVITY. Our analysis showed that known ligand binding sites could be well recovered. We grouped the predicted binding sites according to their similarity which can be used in protein function prediction and drug repurposing studies. Novel binding sites in highly reliable predicted structure regions provide new opportunities for drug discovery. Our CavitySpace is freely available and provides a valuable tool for drug discovery and protein function studies.

The ligand binding sites of a protein provide useful information to uncover its functions and to direct the structure-based drug design. However, as binding site detection relies on the three-dimensional (3D) structural data of proteins, functional analysis based on protein ligand binding sites is formidable for proteins without structural information. Recent developments in protein structure prediction and the 3D structures built by AlphaFold provide an unprecedented opportunity for analyzing ligand binding sites in human proteins. We have used the reliable ligand binding site detection program CAVITY to analyse all the proteins in the human proteome and constructed the CavitySpace database, which is the first pocket library for predicted protein structures. CavitySpace can be used to predict protein function based on pocket information, to identify new druggable protein targets for drug design, and to search for new binding sites for known drugs for drug repurposing. CavitySpace is freely available at http://www.pkumdl.cn:8000/cavityspace/.