Structure-based computational analysis of protein binding sites for function and druggability prediction

Protein binding sites are the places where molecular interactions occur. Thus, the analysis of protein binding sites is of crucial importance to understand the biological processes proteins are involved in. Herein, we focus on the computational analysis of protein binding sites and present structure-based methods that enable function prediction for orphan proteins and prediction of target druggability. We present the general ideas behind these methods, with a special emphasis on the scopes and limitations of these methods and their validation. Additionally, we present some successful applications of computational binding site analysis to emphasize the practical importance of these methods for biotechnology/bioeconomy and drug discovery.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Binding site analyses allow function de-orphanization and druggability prediction. ► We describe how to best characterize and compare protein binding sites. ► We summarize descriptors and methods for druggability prediction. ► Prospective applications of function and druggability prediction are presented. ► Scopes and limitations of structure-based analyses of binding sites are discussed.