Predictive QSAR models development and validation for human ether-a-go-go related gene (hERG) blockers using newer tools

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Hari Narayana Moorthy, NSHN (Author) Other; Maria J Ramos (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: Journal of Enzyme Inhibition and Medicinal Chemistry

Vol. 29

Pages: 317-324

ISSN: 1475-6366

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 11 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-009-D9Z

DOI: 10.3109/14756366.2013.779264

Abstract (EN): In the present computational analysis, pharmacophore-based active conformer selection method was used to derive active conformers for the physicochemical descriptors calculation. The significant regression models were validated using different validation methods, which provided significant Q(2) values. The distance-based approaches were also used to analyze the discriminant property of the molecules contributed in the models. The Mahalanobis distance (MD) values obtained from these studies revealed that the compounds with very high and very low acting human ether-a-go-go-related gene blockers possessed high MD values, while the predicted activity of those compounds exhibited less residual errors. The results obtained in the studies suggest that the distance-based approaches can be used to validate the quantitative structure-activity relationship models significantly. The descriptors contributed in the models explain that the flexibility of the bonds connected to the aromatic rings or non-polar region of the molecules make pi-pi interaction with the aromatic residues of the protein.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8