Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Pharmacophore-Based Virtual Screening

Author(s): Hongmao Sun.

Abstract:

Virtual screening (VS) is an important component of cheminformatics and molecular modeling. An abundance of structural information, indicated by both the ever-increasing availability of 3-dimensional (3D) protein structures and the readiness of free conformational databases of commercially available compounds, such as ZINC, supplies a broad platform for VS. At the same time, new technology enables the implementation of more accurate and sophisticated pharmacophore models and the screening of millions of compounds within a manageable period. Therefore, VS is expected to play a more important role in future drug discovery efforts. This paper will examine and compare the advantages and disadvantages of VS against experimental high-throughput screening (HTS). It will also evaluate pharmacophore-based VS against docking-based VS. The strategies leading to successful pharmacophore-based VS are outlined, including how to enumerate a conformational database efficiently, how to select chemical features for a specific pharmacophore model, how to incorporate excluded volumes to enhance the geographical restrictions, and how to optimize a pharmacophore model. Successful examples of pharmacophore-based VS will be presented.

Keywords: Virtual screening, pharmacophore, molecular docking, HTS

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Article Details

VOLUME: 15
ISSUE: 10
Year: 2008
Page: [1018 - 1024]
Pages: 7
DOI: 10.2174/092986708784049630
Price: $58