Pocket to concavity: a tool for the refinement of protein–ligand binding site shape from alpha spheres

SUMMARY: Understanding the binding site of the target protein is essential for rational drug design. Pocket detection software predicts the ligand binding site of the target protein; however, the predicted protein pockets are often excessively estimated in comparison with the actual volume of the bound ligands. This study proposes a refinement tool for the pockets predicted by an alpha sphere-based approach, Pocket to Concavity (P2C). P2C is divided into two modes: Ligand-Free (LF) and Ligand-Bound (LB) modes. The LF mode provides the shape of the deep and druggable concavity where the core scaffold can bind. The LB mode searches the deep concavity around the bound ligand. Thus, P2C is useful for identifying and designing desirable compounds in Structure-Based Drug Design (SBDD). AVAILABILITY AND IMPLEMENTATION: Pocket to Concavity is freely available at https://github.com/genki-kudo/Pocket-to-Concavity. This tool is implemented in Python3 and Fpocket2.