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多药耐药性RND外排泵的分子动力学计算机模拟

Molecular Dynamics Computer Simulations of Multidrug RND Efflux Pumps.

作者信息

Ruggerone Paolo, Vargiu Attilio V, Collu Francesca, Fischer Nadine, Kandt Christian

机构信息

Department of Physics, University of Cagliari, Cittadella Universitaria S.P. Monserrato-Sestu Km 0.700, 09042 Monserrato (CA), Cagliari, Italy ; CNR-IOM, Unità SLACS, S.P. Monserrato-Sestu Km 0.700, I-09042 Monserrato (CA), Italy.

Departement fu r Chemie und Biochemie, Universita t Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.

出版信息

Comput Struct Biotechnol J. 2013 Mar 3;5:e201302008. doi: 10.5936/csbj.201302008. eCollection 2013.

DOI:10.5936/csbj.201302008
PMID:24688701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3962194/
Abstract

Over-expression of multidrug efflux pumps of the Resistance Nodulation Division (RND) protein super family counts among the main causes for microbial resistance against pharmaceuticals. Understanding the molecular basis of this process is one of the major challenges of modern biomedical research, involving a broad range of experimental and computational techniques. Here we review the current state of RND transporter investigation employing molecular dynamics simulations providing conformational samples of transporter components to obtain insights into the functional mechanism underlying efflux pump-mediated antibiotics resistance in Escherichia coli and Pseudomonas aeruginosa.

摘要

耐药结节化分裂（RND）蛋白超家族多药外排泵的过度表达是微生物对药物产生耐药性的主要原因之一。了解这一过程的分子基础是现代生物医学研究的主要挑战之一，涉及广泛的实验和计算技术。在这里，我们回顾了利用分子动力学模拟对RND转运蛋白的研究现状，该模拟提供了转运蛋白组件的构象样本，以深入了解大肠杆菌和铜绿假单胞菌中由外排泵介导的抗生素耐药性的功能机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/59c2f230e425/CSBJ-5-e201302008-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/27dc4a580367/CSBJ-5-e201302008-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/e611edc08ae7/CSBJ-5-e201302008-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/af5d52c79826/CSBJ-5-e201302008-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/ecf0854c8f36/CSBJ-5-e201302008-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/59c2f230e425/CSBJ-5-e201302008-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/27dc4a580367/CSBJ-5-e201302008-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/e611edc08ae7/CSBJ-5-e201302008-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/af5d52c79826/CSBJ-5-e201302008-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/ecf0854c8f36/CSBJ-5-e201302008-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ba/3962194/59c2f230e425/CSBJ-5-e201302008-g005.jpg

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Recognition of imipenem and meropenem by the RND-transporter MexB studied by computer simulations.
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