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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.
| Abbreviations | ||
| 3-D | = | three-dimensional |
| a.a | = | Amino acid |
| BLAST | = | Basic local alignment search tool |
| AMBER | = | Assisted Model Building with Energy Refinement |
| CDS | = | coding sequence |
| CID | = | Compound identification number |
| DOPE | = | Discrete optimized protein energy |
| GnRH | = | Gonadotropin-releasing hormone |
| GPR54 | = | G protein-coupled receptor 54 |
| GROMACS | = | Groningen Machine for Chemicals Simulations |
| GUI | = | Graphical user interface |
| HPG | = | Hypothalamic-pituitary-gonadal |
| Kiss1r | = | kisspeptin1 receptor |
| kiss2r | = | kisspeptin2 receptor |
| MEGA | = | Molecular Evolutionary Genetics Analysis. |
| MD | = | Molecular dynamics |
| NCBI | = | National Center for Biotechnology Information |
| ORF | = | Open reading frame |
| PDB | = | Protein Data Bank |
| RMSD | = | Root-mean-square deviation |
| SBDD | = | Structure-based drug designing |
| TMDs | = | Transmembrane domains |
| YASARA | = | Yet Another Scientific Artificial Reality Application |
Communicated by Ramaswamy H. Sarma
Disclosure statement
No potential conflict of interest was reported by the authors.