title: Identification of natural inhibitors against angiotensin I converting enzyme for cardiac safety using induced fit docking and MM-GBSA studies.
abstract: BACKGROUND
  Cleistanthins A and B are isolated compounds from the leaves of Cleistanthus collinus Roxb (Euphorbiaceae). This plant is poisonous in nature which causes cardiovascular abnormalities such as hypotension, nonspecific ST-T changes and QTc prolongation. The biological activity predictions spectra of the compounds show the presence of antihypertensive, diuretic and antitumor activities.
  
  
  OBJECTIVE
  Objective of the present study was to determine the in silico molecular interaction of cleistanthins A and B with Angiotensin I- Converting Enzyme (ACE-I) using Induced Fit Docking (IFD) protocols.
  
  
  METHODS
  All the molecular modeling calculations like IFD docking, binding free energy calculation and ADME/Tox were carried out using Glide software (Schrödinger LLC 2009, USA) in CentOS EL-5 workstation.
  
  
  RESULTS
  The IFD complexes showed favorable docking score, glide energy, glide emodel, hydrogen bond and hydrophobic interactions between the active site residues of ACE-I and the compounds. Binding free energy was calculated for the IFD complexes using Prime MM-GBSA method. The conformational changes induced by the inhibitor at the active site of ACE-I were observed based on changes of the back bone Cα atoms and side-chain chi (x) angles. The various physicochemical properties were calculated for these compounds. Both cleistanthins A and B showed better docking score, glide energy and glide emodel when compared to captopril inhibitor.
  
  
  CONCLUSIONS
  These compounds have successively satisfied all the in silico parameters and seem to be potent inhibitors of ACE-I and potential candidates for hypertension.
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, University of Madras, Maraimalai (Guindy) Campus, Chennai, India.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Vijayakumar
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India ; Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology University, Bedong Semeling Road, Bedong, 08100, Kedah, Malaysia, India.
authors.forename: Subramani
authors.initials: S
authors.lastname: Parasuraman
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Raveendran
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, University of Madras, Maraimalai (Guindy) Campus, Chennai, India ; Bioinformatics Infrastructure Facility, University of Madras, Maraimalai (Guindy) Campus, Chennai, India.
authors.forename: Devadasan
authors.initials: D
authors.lastname: Velmurugan
keywords: ADME/Tox; Chi angles; Cleistanthin A; Cleistanthin B; Induced fit docking; Prime MM-GBSA