On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data

Paul Lewis; Marc de Jonge; Frits Daeyaert; Luc Koymans; Maarten Vinkers; Jan Heeres; Paul Janssen; Eddy Arnold; Kalyan Das; Art Clark Jr; Stephen Hughes; Paul Boyer; Marie-Pierre de Béthune; Rudi Pauwels; Koen Andries; Mike Kukla; Donald Ludovici; Bart De Corte; Robert Kavash; Chih Ho

doi:10.1023/A:1025313705564

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On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data

Journal article

Peer reviewed

On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data

Paul Lewis, Marc de Jonge, Frits Daeyaert, Luc Koymans, Maarten Vinkers, Jan Heeres, Paul Janssen, Eddy Arnold, Kalyan Das, Art Clark Jr, …

Journal of computer-aided molecular design, Vol.17(2), pp.129-134

02/2003

DOI: https://doi.org/10.1023/A:1025313705564

PMID: 13677481

Abstract

X-ray crystallography

Chemistry

HIV

Physical Chemistry

molecular modeling

virology

drug design

PLS

statistical analysis

Animal Anatomy / Morphology / Histology

Computer Applications in Chemistry

There are several indications that a given compound or a set of related compounds can bind in different modes to a specific binding site of a protein. This is especially evident from X-ray crystallographic structures of ligand-protein complexes. The availability of multiple binding modes of a ligand in a binding site may present an advantage in drug design when simultaneously optimizing several criteria. In the case of the design of anti-HIV compounds we observed that the more active compounds that are also resilient against mutation of the non-nucleoside binding site of HIV1-reverse transcriptase make use of more binding modes than the less active and resilient compounds.

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Details

Title: On the detection of multiple-binding modes of ligands to proteins, from biological, structural, and modeling data
Creators: Paul Lewis - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Marc de Jonge - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Frits Daeyaert - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Luc Koymans - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Maarten Vinkers - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Jan Heeres - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Paul Janssen - Center for Molecular Design J&JPRD, Janssen Pharmaceutica N.V Vosselaar Belgium
Eddy Arnold - Center for Biotechnology and Medicine, and Chemistry and Chemical Biology Department Rutgers University NJ USA
Kalyan Das - Center for Biotechnology and Medicine, and Chemistry and Chemical Biology Department Rutgers University NJ USA
Art Clark Jr - Center for Biotechnology and Medicine, and Chemistry and Chemical Biology Department Rutgers University NJ USA
Stephen Hughes - NIH-NCI HIV Drug Resistance Program Frederick MD USA
Paul Boyer - NIH-NCI HIV Drug Resistance Program Frederick MD USA
Marie-Pierre de Béthune - Tibotec-Virco Mechelen Belgium
Rudi Pauwels - Tibotec-Virco Mechelen Belgium
Koen Andries - Virology Dept. J&JPRD, Janssen Pharmaceutica N.V Beerse Belgium
Mike Kukla - Chemistry Dept. J&JPRD Spring House PA USA
Donald Ludovici - Chemistry Dept. J&JPRD Spring House PA USA
Bart De Corte - Chemistry Dept. J&JPRD Spring House PA USA
Robert Kavash - Chemistry Dept. J&JPRD Spring House PA USA
Chih Ho - Chemistry Dept. J&JPRD Spring House PA USA
Publication Details: Journal of computer-aided molecular design, Vol.17(2), pp.129-134
Date published: 02/2003
Publisher: Kluwer Academic Publishers
Academic Unit: Center for Advanced Biotechnology and Medicine
Language: English
Resource Type: Journal article
Identifiers: 991031653950004646