title: Molecular dynamics approach to probe PKCβII-ligand interactions and influence of crystal water molecules on these interactions.
abstract: OBJECTIVE
  PKCβII is a potential target for therapeutic intervention against pandemic diabetic complications. Present study probes the molecular interactions of PKCβII with its clinically important ligands, viz. ruboxistaurin, enzastaurin and co-crystallized ligand, 2-methyl-1H-indol-3-yl-BIM-1.
  
  
  METHODS
  The essentials of PKCβII-ligand interaction, crystal water-induced alterations in these interactions and key interacting flexible residues are analyzed. Computational methodologies, viz. molecular docking and molecular simulation coupled with molecular mechanics-Poisson-Boltzmann surface area and generalized born surface area (MM-PB[GB]SA) are employed.
  
  
  RESULTS
  The structural changes in the presence and absence of crystal water molecules in PKCβII ATP binding site residues, and its interaction with bound ligand, are identified. Difference in interaction of selective and nonselective ligand with ATP binding site residues of PKCβII is reported.
  
  
  CONCLUSIONS
  The study showed that the nonbonding interactions contribute significantly in PKCβII-ligand binding and presence of crystal water molecules affects the interactions. The findings of present work may integrate the new aspects in the drug design process of PKCβII inhibitors.
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacoinformatics , Sector 67, S.A.S. Nagar, Punjab 160062 , India +91 172 2211343 ; +91 172 2214692 ; mesophia@niper.ac.in.
authors.forename: Baljinder K
authors.initials: BK
authors.lastname: Grewal
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Bhat
authors.forename: Masilamani Elizabeth
authors.initials: ME
authors.lastname: Sobhia
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D003460:Crystallization; D007211:Indoles / Q000737:chemistry*; D008024:Ligands; D008301:Maleimides / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D007211:Indoles; D008024:Ligands; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D014867:Water; C099154:ruboxistaurin; D000255:Adenosine Triphosphate; D064546:Protein Kinase C beta; C504878:enzastaurin
keywords: crystal water; molecular dynamics; protein kinase C βII inhibitors; protein–ligand interactions; structural features