Combining Structure-Based Drug Design and Pharmacophores

Authors

Renate Griffith, University of Newcastle
T. T. T. Luu, University of Wollongong
James A. Garner, University of WollongongFollow
Paul A. Keller, University of WollongongFollow

RIS ID

12420

Publication Details

This article was originally published as Griffith, R, Luu, TTT, Garner, J & Keller, PA, Combining Structure-Based Drug Design and Pharmacophores, Journal of Molecular Graphics & Modeling , 23(5), 2005, 439-446. Original journal article available here

Abstract

Development towards integrated computer-aided drug design methodologies is presented by utilising crystal structure complexes to produce structure-based pharmacophores. These novel pharmacophores represent the ligand features that are involved in interactions with the target protein, as well as the space around the ligand occupied by the protein. The protein-ligand complexes can also yield information about all interactions that ligands could potentially form with the binding site, as well as about the size of the binding cavity. Together, these describe a 'superligand', which can also be viewed as a pharmacophore. Various types of novel pharmacophores are discussed and compared, using HIV-1 Reverse Transcriptase (RT) as the target protein, and their application in database searching is presented.