Computational Structural Biology, Department of Life Science Informatics B-IT, Life & Medical Sciences Institute, University of Bonn, 53113, Bonn, Germany.
Interdiscip Sci. 2014 Mar;6(1):1-12. doi: 10.1007/s12539-014-0191-3. Epub 2014 Jan 28.
The continuous rise of bacterial resistance against formerly effective pharmaceuticals is a major challenge for biomedical research. Since the first computational studies published seven years ago the simulation-based investigation of antibiotics resistance mediated by multidrug efflux pumps of the resistance nodulation division (RND) protein super family has grown into a vivid field of research. Here we review the employment of molecular dynamics computer simulations to investigate RND efflux pumps focusing on our group's recent contributions to this field studying questions of energy conversion and substrate transport in the inner membrane antiporter AcrB in Escherichia coli as well as access regulation and gating mechanism in the outer membrane efflux ducts TolC and OprM in E. coli and Pseudomonas aeruginosa.
细菌对抗生素的耐药性不断上升，这是生物医学研究面临的主要挑战。自七年前发表第一篇计算研究论文以来，基于模拟的多药外排泵耐药结节分裂（RND）蛋白超家族介导的抗生素耐药性研究已经成为一个活跃的研究领域。在这里，我们回顾了分子动力学计算机模拟在研究 RND 外排泵方面的应用，重点介绍了我们小组在这一领域的最新研究成果，研究了大肠杆菌中内膜反向转运体 AcrB 的能量转换和底物转运问题，以及大肠杆菌和铜绿假单胞菌中外膜外排道 TolC 和 OprM 的进入调节和门控机制。
