title: Pharmacophore mapping based inhibitor selection and molecular interaction studies for identification of potential drugs on calcium activated potassium channel blockers, tamulotoxin.
abstract: BACKGROUND
  Tamulotoxin (TmTx) from Buthus tamulus was found to be a highly venomous toxin which accelerates the neurotransmitter release that directly affects the cardiovascular tissues and the respiratory system leading to death. TmTx from red Indian scorpion is a crucial inhibitor for Ca(2+) activated K(+) channel in humans.
  
  
  OBJECTIVE
  The study is aimed at the identification of potential inhibitors of TmTx through pharmacophore based inhibitor screening and understanding the molecular level interactions.
  
  
  METHODS
  The potential inhibitors for TmTx were identified using pharmacophore model based descriptor information present in existing drugs with the analysis of pharmacokinetic properties. The compounds with good ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) descriptors were subjected to molecular interaction studies. The stability of bound toxin-inhibitor complex was studied using molecular dynamics simulation over a period of one nanosecond.
  
  
  RESULTS
  From a dataset of 3406 compounds, few compounds were selected as potential inhibitors based on the generated best pharmacophore models, pharmacokinetic analysis, molecular docking and molecular dynamics studies.
  
  
  CONCLUSIONS
  In conclusion, two compounds containing better inhibition properties against TmTx are suggested to be better lead molecules for drug development in future and this study will help us to explore more inhibitors from natural origin against tamulotoxin.
authors.affiliation: Department of Bioinformatics, Sathyabama University, Chennai, India.
authors.forename: R Barani
authors.initials: RB
authors.lastname: Kumar
authors.forename: M Xavier
authors.initials: MX
authors.lastname: Suresh
keywords: Absorption; Distribution; Excretion and Toxicity; HipHop; Metabolism; ion channels; molecular docking; pharmacophore; tamulotoxin