Targeting GPR52 for potential agonists for schizophrenia therapy: A computational drug discovery study

G Protein-Coupled Receptors (GPCRs) are one of the most attractive therapeutic targets due to their active role in different systems and disease types. The increasing three-dimensional structure information of GPCRs has made them interesting for Structure-Based Drug Design (SBDD) studies. There are various orphan GPCRs whose endogenous molecules have not yet been identified, although their structural information is known. The recent discovery of the three-dimensional structure of GPR52, an orphan GPCR involved in central nervous system diseases, made it stand out as a drug target. In this study, it is aimed to find a lead drug molecule candidate for GPR52 by using structure-based drug design techniques. The study comprises a set of SBDD methods, including preparation of a small molecule library, pharmacophore modeling, molecular docking, consensus scoring, molecular dynamics simulations, calculation of binding free energy, and in silico pharmacokinetic studies for GPR52. It is expected that the molecules obtained as a result of the study may be strong candidates for in vitro and in vivo experiments or could be used as lead drug molecules in new drug discovery and development studies.