title: Application of the linear interaction energy method for rational design of artemisinin analogues as haeme polymerisation inhibitors.
abstract: The anti-malarial activity of artemisinin-derived drugs appears to be mediated by an interaction of the drug's endoperoxide bridge with intra-parasitic haeme. The binding affinity of artemisinin analogues with haeme were computed using linear interaction energy with a surface generalised Born (LIE-SGB) continuum solvation model. Low levels of root mean square error (0.348 and 0.415 kcal/mol) as well as significant correlation coefficients (r(2) = 0.868 and 0.892) between the experimental and predicted free energy of binding (FEB) based on molecular dynamics and hybrid Monte Carlo sampling techniques establish the SGB-LIE method as an efficient tool for generating more potent inhibitors of haeme polymerisation inhibition.
authors: Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan 173215, Himachal Pradesh, India.
authors: M
authors: M
authors: Srivastava
authors: H
authors: H
authors: Singh
authors: P K
authors: PK
authors: Naik
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006418:Heme / Q000037:antagonists & inhibitors*; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D006418:Heme; C031327:artemisinin