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Bulletin of Pure & Applied Sciences- Chemistry
Year : 2018, Volume : 37c, Issue : 1
First page : ( 53) Last page : ( 63)
Print ISSN : 0970-4620. Online ISSN : 2320-320X.
Article DOI : 10.5958/2320-320X.2018.00008.0

2D and 3D QSAR model generation of CDK4 inhibitors

Divya V1, Pushpa V.L.1,*, Sarithamol S, Manoj K.B1

1Department of Chemistry, Sree Narayana College, Kollam, Kerala, India

*Corresponding Author Pushpa V.L, Department of Chemistry, Sree Narayana College, Kollam, Kerala, India. E-mail: drpushpavl2017@gmail.com

Online published on 28 February, 2018.

Abstract

2D and 3D QSAR studies were applied on a set of CDK4 inhibitors which were assayed by same method to model and understand inhibitory activities. Among the various 2D QSAR models generated, ten models created by Kernel-Based Partial Least Square (kpls) regression method had high scores with an average value 0.8561. Top ranked model kpls_ linear_15 has a score value of 0.8804, R2 0.8947 and Q2 0.8909. This model considers linear fragments and ring closures. Bioactive conformation of the ligand molecules were identified by docking analysis of highly active molecule 2 (pIC50 =8.796) in the Extra Precision mode with CDK4 homology model and the binding affinity was obtained as XP GScore of-8.072 which is the total contribution of coulomic interactions, binding interactions and van der Waals interations. All optimized structures were aligned and an atom based 3D QSAR model was established (R2=0.9651, R2 cv=0.8191 and Q2=0.7368). This model was assigned large contribution of hydrophobic/nonpolar features, electron withdrawing features and hydrogen bond donor features to the biological activity. The influences of these structural features were validated by analyzing the docking results. These outcomes will direct advance structural alteration and prediction of new CDK4 inhibitors.

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Keywords

QSAR, Homology model, CDK4, Docking, Drug design.

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