A new methodology for the simulation of flexible protein-ligand interactions

James Garner; John Deadman; David Rhodes; Renate Griffith; Paul A Keller

doi:10.1016/j.jmgm.2006.11.004

A new methodology for the simulation of flexible protein-ligand interactions

J Mol Graph Model. 2007 Jul;26(1):187-97. doi: 10.1016/j.jmgm.2006.11.004. Epub 2006 Nov 21.

Authors

James Garner¹, John Deadman, David Rhodes, Renate Griffith, Paul A Keller

Affiliation

¹ Department of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia.

PMID: 17229583
DOI: 10.1016/j.jmgm.2006.11.004

Abstract

A methodology has been developed for the simulation of induced fit between a ligand and its target protein. It utilizes constrained molecular dynamics where atoms determined to be immobile from difference distance matrix studies are fixed. Application of this methodology to HIV-1 reverse transcriptase (RT) as the example target protein has demonstrated its robustness. Short simulation times are sufficient to achieve good refinement of docking poses resulting from exchange of structurally dissimilar inhibitors between crystal structures.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkynes
Benzoxazines / chemistry
Computer Simulation
Crystallography, X-Ray
Cyclopropanes
HIV Reverse Transcriptase / chemistry
HIV Reverse Transcriptase / genetics
Ligands
Models, Molecular*
Nevirapine / chemistry
Point Mutation
Protein Conformation
Proteins / chemistry*
Reverse Transcriptase Inhibitors / chemistry
Thermodynamics

Substances

Alkynes
Benzoxazines
Cyclopropanes
Ligands
Proteins
Reverse Transcriptase Inhibitors
Nevirapine
HIV Reverse Transcriptase
efavirenz