Login

Journal Image
Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 15
ISSUE: 10
DOI: 10.2174/092986708784049630      Price:  $58









Pharmacophore-Based Virtual Screening

img
Author(s): Hongmao Sun
Pages 1018-1024 (7)
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
Affiliation:
Department of Discovery Chemistry,Hoffmann-La Roche, Inc., 340 Kingsland Street, Nutley, NJ 07110,USA.