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Structural analysis, molecular docking and molecular dynamics simulations of G-protein-coupled receptor (kisspeptin) in fish.

Abstract：

:Kisspeptins are neuropeptide that has emerged as an essential gatekeeper for reproduction and onset of puberty in higher vertebrates including fish. In present study, structural analysis, molecular docking and molecular dynamics simulations of kisspeptin receptor (kiss2r) were carried out, which is a G-protein-coupled receptor. An open reading frame of kiss2r is 1101 bp encoding a putative protein of 366 amino acids. Secondary structure protein consists of alpha helix 69.70%, beta-turn 2%, disordered 18% and 43% transmembrane helix. Sub-cellular localization and gene ontology revealed kiss2r protein is maximum localized in the plasma membrane (99.1%) with score of 4.958 and gene ontology analysis showed molecular function of 89.8%, biological process 30.6% and cellular component 41.2%. Homology modeling and structure validation of kiss2r confirm 97.5% residues are in the favored region and 2.5% residues are in the allowed region. Virtual screening of ligands and molecular docking revealed 2-(4-(2-Carboxyethyl) phenethylamino) 5'-N-ethylcarboxamidoadenosine and N-ethyl-5'-carboxamido adenosine ligand exhibited highest binding energy values 9.437 and 7.476 kcal/mol. Molecular interactions depict conventional hydrogen bonding with GLU197 THR198 GLN288 HIS297 LYS303 and TYR313 residues. Molecular dynamic simulation results revealed that complex 2 (N-ethyl-5'-carboxamido adenosine and kiss2r protein) is better than complex 1 (2-(4-(2-Carboxyethyl) phenethylamino)-5'-N-ethylcarboxamidoadenosine and kiss2r protein) and its connotation in drug designing. The outcome of this work sheds light on the protein modeling, molecular docking and virtual screening of agonist ligands against kiss2 and thus may significantly contribute in designing and optimizing therapeutic strategies to cure various reproductive dysfunctions in fish. Abbreviations3-Dthree-dimensionala.aAmino acidBLASTBasic local alignment search toolAMBERAssisted Model Building with Energy RefinementCDScoding sequenceCIDCompound identification numberDOPEDiscrete optimized protein energyGnRHGonadotropin-releasing hormoneGPR54G protein-coupled receptor 54GROMACSGroningen Machine for Chemicals SimulationsGUIGraphical user interfaceHPGHypothalamic-pituitary-gonadalKiss1rkisspeptin1 receptorkiss2rkisspeptin2 receptorMEGAMolecular Evolutionary Genetics Analysis.MDMolecular dynamicsNCBINational Center for Biotechnology InformationORFOpen reading framePDBProtein Data BankRMSDRoot-mean-square deviationSBDDStructure-based drug designingTMDsTransmembrane domainsYASARAYet Another Scientific Artificial Reality ApplicationCommunicated by Ramaswamy H. Sarma.

journal_name

J Biomol Struct Dyn

journal_title

Journal of biomolecular structure & dynamics

authors

Rather MA,Dutta S,Guttula PK,Dhandare BC,Yusufzai SI,Zafar MI

doi

10.1080/07391102.2019.1633407

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

2422-2439

issue

eissn

0739-1102

issn

1538-0254

journal_volume

pub_type

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Structural analysis, molecular docking and molecular dynamics simulations of G-protein-coupled receptor (kisspeptin) in fish.