Current Computer-Aided Drug Design

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

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Receptor-Based Pharmacophore and Pharmacophore Key Descriptors for Virtual Screening and QSAR Modeling

Author(s): Xialan Dong, Jerry O. Ebalunode, Sheng-Yong Yang, Weifan Zheng.

Abstract:

The intuitive nature of the pharmacophore concept has made it widely accepted by the medicinal chemistry community, evidenced by the past 3 decades of development and application of computerized pharmacophore modeling tools. On the other hand, shape complementarity has been recognized as a critical factor in molecular recognition between drugs and their receptors. Recent development of fast and accurate shape comparison tools has facilitated the wide spread use of shape matching technologies in drug discovery. However, pharmacophore and shape technologies, if used separately, often lead to high false positive rate. Thus, integrating pharmacophore matching and shape matching technologies into one program has the potential to reduce the false positive rates in virtual screening. Other issues of current pharmacophore technologies include sometimes high false negative rate and non-quantitative prediction. In this article, we first focus on a recently implemented method (Shape4) that combines receptor based shape matching and pharmacophore comparison in a single algorithm to create shape pharmacophore models for virtual screening. We also examine a recent example that utilizes multi-complex information to develop receptor-based pharmacophore models that promises to reduce false negative rate. Finally, we review several methods that employ receptor-based pharmacophore map and pharmacophore key descriptors for QSAR modeling. We conclude by emphasizing the concept of receptor-based shape pharmacophore and its roles in future drug discovery.

Keywords: Pharmacophore, pharmacophore key, QSAR, molecular shape, virtual screening, drug discovery, pharmacophore modeling tools, LigandScout software, topochemical indices triglycerides, lead optimization

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Article Details

VOLUME: 7
ISSUE: 3
Year: 2011
Page: [181 - 189]
Pages: 9
DOI: 10.2174/157340911796504332
Price: $58