Characterization, molecular docking, dynamics simulation and metadynamics of kisspeptin receptor with kisspeptin

Abstract

We report molecular characterization of the kisspeptin receptor (kiss1r), an essential gatekeeper forreproduction and onset of puberty in vertebrates. The full-length cDNA sequence of kiss1r is 1786 bpwhich consist of 5 UTR (untranslated region) 261 bp, 3 UTR of 424 bp and open reading frame of 1101encoding a putative protein of 366 amino acids. Basal tissue expression pattern of kiss1r mRNA revealedthat it is mainly expressed in the brain and testis. We also report the structure of the kiss1r, alongwith plausible activation mechanism of this receptor by kisspeptin using computational modelling anddynamic simulation approach of multiple 100 ns of timescale. A present modelling and simulations stud-ies shed light on the molecular level of interaction, suggesting that direct hydrogen bonds between ASN4,SER5, GLY7, ARG9 and PHE10 of kisspeptin and TRP7, ASN8, GLU11, ILE17, ASN19 and TYR183 of kiss1rcould be crucial role players in initial binding of receptor and the kisspeptin towards allosteric modulatoryeffects of kisspeptin on the receptor. To the best our knowledge, this is the first report on computationalmodelling and molecular dynamic simulations of kiss1r in animals shedding light on its possible mode ofactivation.