QSAR analyses of organophosphates for insecticidal activity and its in-silico validation using molecular docking study.
The present work was carried out to design and develop novel QSAR models using 2D-QSAR and 3D-QSAR with CoMFA methodology for prediction of insecticidal activity of organophosphate (OP) molecules. The models were validated on an entirely different external dataset of in-house generated combinatorial library of OPs, by completely different computational approach of molecular docking against the target AChE protein of Musca domestica. The dock scores were observed to be in good correlation with 2D-QSAR and 3D-QSAR with CoMFA predicted activities and had the correlation coefficients (r(2)) of -0.62 and -0.63, respectively. The activities predicted by 2D-QSAR and 3D-QSAR with CoMFA were also observed to be highly correlated with r(2)=0.82. Also, the combinatorial library molecules were screened for toxicity in non-target organisms and degradability using USEPA-EPI Suite. The work was first step towards computer aided design and development of novel OP pesticide candidates with good insecticidal property but lower toxicity in non-targeted organisms and having biodegradation potential.
Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak 124001, Haryana, India.
Ravi Ranjan Kumar
RR
Niraj
Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak 124001, Haryana, India.
Vandana
V
Saini
Toxicology and Computational Biology Group, Centre for Bioinformatics, M.D. University, Rohtak 124001, Haryana, India. Electronic address: akumar.cbt.mdu@gmail.com.
Ajit
A
Kumar
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D006793:Houseflies / Q000187:drug effects / Q000201:enzymology*; D019476:Insect Proteins / Q000037:antagonists & inhibitors; D007306:Insecticides / Q000737:chemistry* / Q000633:toxicity; D062105:Molecular Docking Simulation; D010755:Organophosphates / Q000737:chemistry* / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000633:toxicity
D019476:Insect Proteins; D007306:Insecticides; D010755:Organophosphates; D054852:Small Molecule Libraries; D000110:Acetylcholinesterase
CoMFA; Combinatorial library; EPI Suite; Homology modelling