Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


QSAR Models for the Reactivation of Sarin Inhibited Acetylcholinesterase by Quaternary Pyridinium Oximes Based on Monte Carlo Method

Author(s): Aleksandar M. Veselinovic, Jovana B. Veselinovic, Andrey A. Toropov, Alla P. Toropova, Goran M. Nikolic.


Monte Carlo method has been used as a computational tool for building QSAR models for the reactivation of sarin inhibited acetylcholinesterase (AChE) by quaternary pyridinium oximes. Simplified molecular input line entry system (SMILES) together with hydrogen-suppressed graph (HSG) was used to represent molecular structure. Total number of considered oximes was 46 and activity was defined as logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M. One-variable models have been calculated with CORAL software for one data split into training, calibration and test set. Computational experiments indicated that this approach can satisfactorily predict the desired endpoint. Best QSAR model had the following statistical parameters: for training set r2 = 0.7096, s = 0.177, MAE = 0.148; calibration set: r2 = 0.6759, s = 0.330, MAE = 0.271 and test set: r2 = 0.8620, s = 0.182, MAE = 0.150. Structural indicators (SMILES based molecular fragments) for the increase and the decrease of the stated activity are defined. Using defined structural alerts computer aided design of new oxime derivatives with desired activity is presented.

Keywords: AChE reactivator, Chemoinformatics, CORAL, Drug design, oximes, QSAR, SMILES.

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Article Details

Year: 2014
Page: [266 - 273]
Pages: 8
DOI: 10.2174/1574886309666141126144848
Price: $58