title: Molecular Modeling and Dynamics Simulation Analysis of KATNAL1 for Identification of Novel Inhibitor of Sperm Maturation.
abstract: BACKGROUND
  Hormone based birth control often causes various side effects. A recent study revealed that temporary infertility without changing hormone levels can be attained by inhibiting Katanin p60 ATPase-containing subunit A-like 1 protein (KATNAL1) which is critical for sperm maturation in the testes.
  
  
  OBJECTIVE
  This study aimed at attaining the most energetically stable three dimensional (3D) structure of KATNAL1 protein using comparative modeling followed by screening of a ligand library of known natural spermicidal compounds for their binding affinity with KATNAL1. This in turn may inhibit the development of mature sperm in the seminiferous epithelium.
  
  
  METHODS
  A series of computational techniques were used for building the 3D structure of KATNAL1 which was further optimized by molecular dynamics (MD) simulation. For revealing the ATP binding mode of KATNAL1, docking study was carried out using the optimized model obtained from the MD simulation. The docking study was also employed to test the binding efficiency of the ligand library.
  
  
  RESULTS
  Molecular docking study confirmed the ATP binding of KATNAL1 with various hydrophobic and hydrogen bond interactions. Binding efficiency of the ligand library suggested that calotropin, a cardenolide of Calotropis procera showed the highest binding efficiency against the target protein without toxicity. MD simulation of the docked complex validated the results of the docking study.
  
  
  CONCLUSIONS
  This study revealed the ATP binding mode of KATNAL1 and identified calotropin as a potential lead molecule against it showing high binding efficiency with good bioavailability and no mutagenicity. Further in vitro and in vivo bioassay of calotropin could facilitate the development of novel non-hormonal male-specific contraceptive in near future.
authors.affiliation: Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam. India.
authors.forename: Kishore
authors.initials: K
authors.lastname: Sarma
authors.affiliation: Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam. India.
authors.forename: Shubhadeep
authors.initials: S
authors.lastname: Roychoudhury
authors.affiliation: Centre for Studies in Biotechnology, Dibrugarh University, Dibrugarh 786004, Assam. India.
authors.forename: Sudipta Sankar
authors.initials: SS
authors.lastname: Bora
authors.affiliation: Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam. India.
authors.forename: Budheswar
authors.initials: B
authors.lastname: Dehury
authors.affiliation: Centre for Studies in Biotechnology, Dibrugarh University, Dibrugarh 786004, Assam. India.
authors.forename: Pratap
authors.initials: P
authors.lastname: Parida
authors.affiliation: Centre for Studies in Biotechnology, Dibrugarh University, Dibrugarh 786004, Assam. India.
authors.forename: Saurav
authors.initials: S
authors.lastname: Das
authors.affiliation: Centre for Bioinformatics Studies, Dibrugarh University, Dibrugarh 786004, Assam. India.
authors.forename: Robin
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, Assam. India.
authors.forename: Chandrajit
authors.initials: C
authors.lastname: Dohutia
authors.affiliation: Department of Life Science and Bioinformatics, Assam University, Silchar 788011, Assam. India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Nath
authors.affiliation: Bioinformatics Centre, Guru Charan College, Silchar 788 004, Assam. India.
authors.forename: Bibhas
authors.initials: B
authors.lastname: Deb
authors.affiliation: Distributed Information Centre, Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat 785013, Assam. India.
authors.forename: Mahendra K
authors.initials: MK
authors.lastname: Modi
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D002298:Cardenolides / Q000494:pharmacology; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D000074201:Katanin; D008024:Ligands; D008297:Male; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000494:pharmacology; D013079:Sperm Maturation / Q000187:drug effects*
chemical_list: D002298:Cardenolides; D003272:Contraceptive Agents, Male; D008024:Ligands; D054852:Small Molecule Libraries; C546414:calotropin; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C000600349:KATNAL1 protein, human; D000074201:Katanin
keywords: KATNAL1; docking; homology modeling; molecular dynamics simulation; non-hormonal contraceptive; sperm maturation