Classification of Plasmodium falciparum glucose-6-phosphate dehydrogenase inhibitors by support vector machine
- PDF / 322,484 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 109 Downloads / 210 Views
FULL-LENGTH PAPER
Classification of Plasmodium falciparum glucose-6-phosphate dehydrogenase inhibitors by support vector machine Xiaoli Hou · Aixia Yan
Received: 20 January 2013 / Accepted: 22 April 2013 / Published online: 9 May 2013 © Springer Science+Business Media Dordrecht 2013
Abstract Plasmodium falciparum glucose-6-phosphate dehydrogenase (PfG6PD) has been considered as a potential target for severe forms of anti-malaria therapy. In this study, several classification models were built to distinguish active and weakly active PfG6PD inhibitors by support vector machine method. Each molecule was initially represented by 1,044 molecular descriptors calculated by ADRIANA.Code. Correlation analysis and attribute selection methods in Weka were used to get the best reduced set of molecular descriptors, respectively. The best model (Model 2w) gave a prediction accuracy (Q) of 93.88 % and a Matthew’s correlation coefficient (MCC) of 0.88 on the test set. Some properties such as σ atom charge, π atom charge, and lone pair electronegativityrelated descriptors are important for the interaction between the PfG6PD and the inhibitor. Keywords Plasmodium falciparum glucose-6-phosphate dehydrogenase (PfG6PD) inhibitor · Classification · Support vector machine (SVM) · Kohonen’s self-organizing map (SOM)
Introduction Malaria is one of the most severe infectious diseases with 240 million cases in 2009 [1]. This common disease is caused Electronic supplementary material The online version of this article (doi:10.1007/s11030-013-9447-9) contains supplementary material, which is available to authorized users. X. Hou · A. Yan (B) State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, P.O. Box 53, Beijing 100029, China e-mail: [email protected]; [email protected]
by protozoa of the genus Plasmodium, and it is delivered by the bites of anopheles mosquitoes [2]. Severe forms of the disease are mainly caused by Plasmodium falciparum parasite which is commonly treated by drugs focusing on its erythrocytic phase [3]. Glucose-6-phosphate dehydrogenase (G6PD) is known as a potential novel target for anti-malaria drugs [4,5]. G6PD is the rate-limiting enzyme that catalyzes the first step of the pentose phosphate pathway (PPP), and this pathway is crucial either for human blood red cells or the malaria parasite. Moreover, it is the only enzyme responsible for the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH), and a key factor in various redox and anti-oxidant systems. G6PD is also critical for the generation of ribose 5-phosphate, which is an essential precursor for the de novo synthesis of RNA and DNA [1,6]. To date, only a small number of anti-malaria drugs have been reported, and most drugs belong to either the quinoline or the antifolate class. Recently, the artemisinin derivatives have been used but mostly in Southeast Asia. Several marketed drugs for anti-malaria theraphies, such as chloroq
Data Loading...
