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Computational Tools for the Analysis and Visualization of Multiple Protein-Ligand Complexes.

O'Brien, Sean E., Brown, David G., Mills, James E., Phillips, Chris, Morris, Gregg (2005) Computational Tools for the Analysis and Visualization of Multiple Protein-Ligand Complexes. Journal of Molecular Graphics and Modelling, 24 (3). pp. 186-194. ISSN 1093-3263. (doi:10.1016/j.jmgm.2005.08.003) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1016/j.jmgm.2005.08.003

Abstract

Modern methods in genomics and high-throughput crystallography have ensured that we have access to a large and rapidly increasing, number of X-ray structures of protein-ligand complexes. A structure-based approach to drug design aims to exploit this information, but current methods are not suited to the examination of the large numbers of complexes available. We present computational tools that analyse and display multiple protein-ligand interactions and their properties in a simplified way. We illustrate how a novel binding-mode similarity metric is able to cluster 20 ligands complexed to HIV-1 reverse transcriptase into distinct groups. The properties of each cluster are then projected onto a group surface as a series of color gradients. Analysis of these surfaces reveals fundamental similarities and differences in the binding modes of these diverse compounds. In addition, the simplicity of the surface representations facilitates the transfer of information between the crystallographer, computational chemist and the chemist. We also show how two- and three-dimensional (2- and 3-D) similarities can be combined to provide enhanced understanding of 33 factor Xa inhibitor complexes. This methodology has enabled us to identify pharmaceutically relevant relationships between ligands and their binding modes that had previously been hidden in a wealth of data.

Item Type: Article
DOI/Identification number: 10.1016/j.jmgm.2005.08.003
Uncontrolled keywords: X-ray structure; Binding mode; Ligand–protein interaction; Surface visualization; HIV-1 reverse transcriptase; Factor Xa
Subjects: Q Science > QD Chemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: David Brown
Date Deposited: 11 Jun 2013 13:38 UTC
Last Modified: 29 May 2019 10:17 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34262 (The current URI for this page, for reference purposes)
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