title: Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.
abstract: The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds.
authors.affiliation: Medical & Biological Computing Laboratory, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
authors.forename: Mahalakshmi
authors.initials: M
authors.lastname: Thillainayagam
authors.affiliation: Medical & Biological Computing Laboratory, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
authors.forename: Anand
authors.initials: A
authors.lastname: Anbarasu
authors.affiliation: Medical & Biological Computing Laboratory, School of Biosciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India. Electronic address: sudhaanand@vit.ac.in.
authors.forename: Sudha
authors.initials: S
authors.lastname: Ramaiah
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000737:chemistry; D057056:Cysteine Proteases / Q000378:metabolism*; D016503:Drug Delivery Systems; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000201:enzymology*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
chemical_list: D000962:Antimalarials; D002599:Chalcone; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases; C416224:falcipain 2
keywords: Aryl chalcone derivatives; CoMFA; Cysteine protease inhibitors; Falcipain -2; Molecular docking