Prediction and design study of candidate drug molecules for G protein-coupled receptors using computer aided drug design methods

The discovery and design of a drug is a complex process that requires a lot of time and cost. With the advancement of technology and computational power, Computer- Aided Drug Design approaches have become more critical in drug discovery and design and overcome the limitations of traditional methods. 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 many orphan GPCRs whose endogenous molecules have not yet been identified, although their structural information is known. The discovery of the three-dimensional structure of GPR52, an orphan GPCR involved in central nervous system diseases, in 2020 made it stand out as a drug target. In this thesis study, it is aimed to find a possible lead drug molecule candidate for GPR52 by using structure-based drug design techniques. The study comprises many SBDD methods including preparation of a small molecule library, pharmacophore modelling, 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 candidates for in vitro and in vivo experiments or could be used as lead drug molecule candidates in new drug discovery and development studies.