VIRTUAL TARGET CONSTRUCTION FOR STRUCTURE-BASED SCREENING IN THE DISCOVERY OF HISTAMINE H2 RECEPTOR LIGANDS

Objective: This study aimed to develop validated targets to be employed in structure-based virtual screening (SBVS) to discover ligands for the human histamine H2 receptor (hHRH2). Methods: The virtual targets construction was initiated by homology modeling with the reference compound ranitidine as the ligand followed by 100 ns molecular dynamics (MD) simulations. During MD simulations, the snapshot with the lowest value of the free energy of binding was selected for further validation by re-docking simulations. All simulations were performed in YASARA-Structure. Results: The research presented here resulted in one validated target for the SBVS. Additionally, by employing a clustering module in MD simulations analysis in YASARA-Structure, more than ten different virtual targets are also available for further uses. Conclusion: The virtual targets resulted in this research offer possibilities to construct valid SBVS protocols to identify ligands for the hHRH2.