High end GPCR design: crafted ligand design and druggability analysis using protein structure lipophilic hotspots and explicit water networks

摘要

PurposeG Protein-Coupled Receptors (GPCRs) are a large family of therapeutically important proteins and as diverse X-ray structures become available it is increasingly possible to leverage structural information for rational drug design.We present herein approaches that use explicit water networks combined with energetic surveys of the binding site (GRID), providing an enhanced druggability and ligand design approach, with structural understanding of ligand binding, including a ‘magic’ methyl and binding site mutations, and a fast new approach to generate and score waters.