Virtual screening of molecular compounds targeting human OPN5 protein

Summary: Abstract Body: Neuropsin (OPN5) is an opsin family member known to function as a photopigment responsive to wavelengths in the near UV (λmax = 380 nm). OPN5 studies started with the initial cloning of human OPN5 and mouse OPN5, regulates seasonal breeding behaviour in birds and the activity cycle, mediates photoentrainment of the retinal circadian clock and regulates vascular regression timing in mice. but also mediate light dependent melanin synthesis in humn skin melanocytes. In summary, the function of OPN5 in organ tissues has been well characterized. However, the molecular compound inhibitors of human OPN5 protein are not yet clear. This study aims to explore molecular inhibitors targeting Human OPN5 protein. To explore molecular compounds targeting Human OPN5 protein, the software used for virtual screening in this project is Schrödinger Maestro 12.8 and the 3D drawing software is PyMol. The flowchart is as follows: Download the 3D structure of Human OPN5 from the AlphaFold database (AlphaFold ID:AF-Q6U736-F1). Use Protein Preparation Wizard modules to hydrogenate, followed by energy optimization Transform. Set the box size to 20 Å x 20 Å x 20 Å with LYS296 as the center. Using Schrödinger software to perform hydrogenation, energy optimization, and other treatments on small molecule compounds, followed by virtual screening using 3D structures. Finally, we will import the prepared small molecule compounds and use the Glide module for molecular docking, where the receptor and ligand molecules dock with each other through geometric and energy matching. Our studies showed that the top five compounds(HY-W013093, Docking score：15.547; HY-N4310, Docking score:14.329; HY-Q29623, Docking score：12.995; HY-Q43805,Docking score:12.403; HY-Q36970,Docking score:12.327) for further research based on their docking score values. This study laid the experimental foundation for the development of OPN5 inhibitors. Yinghua Lan¹, Yu Wang¹, Hongguang Lu¹ 1. Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, China. Translational Studies: Cell and Molecular Biology