Violina T. Angelovaa
Institute of Neurobiology, Bulgaria
Title: Molecular dynamics model of melatonin and MT1 receptor
Biography
Biography: Violina T. Angelovaa
Abstract
Melatonin receptor (MT1) is an attractive target for elaboration of new drug candidates, but unfortunately is known to be unstable out of the membrane lipid bilayer which makes the obtaining of a crystal structure by X-Ray diffraction (XRD) an elusive goal. Up to now there is no published real structure, suitable for docking of new ligands targeting this receptor. However, there are lots of models based on the data from crystallized rhodopsin, but they are too artificial for reasonable docking of drug-like candidate molecules. To overcome these drawbacks we built an in silico molecular model of a melatonin receptor in membrane bilayer in water cell, with explicit water molecules. For that purpose we used GROMACS molecular mechanics software with GROMOS force field and TYP3P water model. Calculations were carried out in periodic boundary conditions at 300 K and 1 bar pressure, physiological NaCl content and pH 7.
By the simulation we caught the act of melatonin entering the receptor which enlightened a wide variety of interactions that can facilitate or to disturb the movement of melatonin to the hardly accessible active site of MT1. Ðœolecular docking of the drug like candidates was performed on receptor model. The information can be used along with data obtained from the structure of melatonin-receptor complex to construct new analogs of melatonin, capable not only to activate the receptor but also to successfully manage their way to the MT1 binding site. Application grant: DH13/16, 21.12.2017.