Molecular modeling and simulation of Mycobacterium tuberculosis cell wall permeability

Biomacromolecules
Xuan Hong, A J Hopfinger

Abstract

The low permeability of the mycobacterial cell wall is thought to contribute to the intrinsic drug resistance of mycobacteria. In this study, the permeability of the Mycobacterium tuberculosis cell wall is studied by computer simulation. Thirteen known drugs with diverse chemical structures were modeled as solutes undergoing transport across a model for the M. tuberculosis cell wall. The properties of the solute-membrane complexes were investigated by means of molecular dynamics simulation, especially the diffusion coefficients of the solute molecules inside the cell wall. The molecular shape of the solute was found to be an important factor for permeation through the M. tuberculosis cell wall. Predominant lateral diffusion within, as opposed to transverse diffusion across, the membrane/cell wall system was observed for some solutes. The extent of lateral diffusion relative to transverse diffusion of a solute within a biological cell membrane may be an important finding with respect to absorption distribution, metabolism, elimination, and toxicity properties of drug candidates. Molecular similarity measures among the solutes were computed, and the results suggest that compounds having high molecular similarity will display simi...Continue Reading

Citations

Oct 30, 2012·Bioinformatics·Benjamin MergetChristoph A Sotriffer
Dec 19, 2006·Journal of Molecular Biology·Sudharsan SridharanJames C Sacchettini
Nov 22, 2007·Molecular Microbiology·Alessandro CascioferroRiccardo Manganelli
Jan 13, 2006·Journal of Molecular Graphics & Modelling·Rudolf Kiralj, Márcia M C Ferreira
Dec 24, 2013·Chemistry and Physics of Lipids·Wilma GroenewaldAnna K Croft
May 29, 2016·European Journal of Medicinal Chemistry·Anna AdamskaAgnieszka B Olejniczak
Jan 7, 2017·PLoS Computational Biology·Pia Abel Zur WieschTed Cohen

Related Concepts

Cell Membrane Permeability
Cell Wall
Mycobacterium tuberculosis H37Rv
Quantitative Structure Property Relationship

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