SiteRadar: Utilizing Graph Machine Learning for Precise Mapping of Protein-Ligand-Binding Sites.

Abstract

Identifying ligand-binding sites on the protein surface is a crucial step in the structure-based drug design. Although multiple techniques have been proposed, including those using machine learning algorithms, the existing solutions do not provide significant advantages over nonmachine learning approaches and there is still a big room for improvement. The low ability to identify protein-ligand-binding sites makes available approaches inapplicable to automated drug design. Here, we present SiteRadar, a new algorithm for mapping cavities that are likely to bind a small-molecule ligand. SiteRadar shows higher accuracy in binding site identification compared with FPocket and PUResNet. SiteRadar demonstrates an ability to detect up to 74% of true ligand-binding sites according to the top N + 2 metric and usually covers approximately 80% of ligand atoms. Therefore, SiteRadar can be regarded as a promising solution for implementation into algorithms for automated drug design.