Title: Development of 3D-QSAR combination approach for discovering and analysing neuraminidase inhibitors in silico

Authors: Chun-Yuan Lin; Hsiao-Chieh Chi; Kuei-Chung Shih; Jiayi Zhou; Nai-Wan Hsiao; Chuan-Yi Tang

Addresses: Department of Computer Science and Information Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan 33302, ROC; Research Centre for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan,Taiwan 33302, ROC ' Department of Computer Science and Information Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan 33302, ROC ' Department of Computer Science, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013, ROC ' Department of Computer Science, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013, ROC ' Institute of Biotechnology, National Changhua University of Education, No.1, Jin-De Road, Changhua, Taiwan 50007, ROC ' Department of Computer Science, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan 30013, ROC; Department of Computer Science and Information Engineering, Providence University, 200 Chung-Chi Rd., Salu Dist., Taichung, Taiwan 43301, ROC

Abstract: Zanamivir and Oseltamivir are both sialic acid analog inhibitors of Neuraminidase (NA), which is an important target in influenza A virus treatment. Quantitative Structure-Activity Relationships (QSAR) is a common computational method for correlating the structural properties of compounds (or inhibitors) with their biological activities. The pharmcophore model easily and quickly recognises related inhibitors and also fits the binding site interaction features of a protein structure. The Comparative Molecular Similarity Index Analysis (CoMSIA) model easily optimises molecular structures and describes the limit range of molecule weights. This study proposes a combination approach that integrates these two models based on the same training set inhibitors in order to screen and optimize NA inhibitor candidates during drug design.

Keywords: QSAR; quantitative structure-activity relationships; theoretical pharmcophore; ligand pharmcophore; CoMSIA; comparative molecular similarity index analysis; influenza A virus; flu virus; computer-aided drug design; Fischer cross validation test; PLS; partial least squares; leave-one-out; LOO; contour map; neuraminidase inhibitors; molecular structures; molecule weights.

DOI: 10.1504/IJDMB.2014.060053

International Journal of Data Mining and Bioinformatics, 2014 Vol.9 No.3, pp.305 - 320

Received: 16 Feb 2012
Accepted: 16 Feb 2012
Published online: 21 Oct 2014 *

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