用布朗动力学研究氨基糖苷类抗生素与核糖体A位点的关联。
Association of aminoglycosidic antibiotics with the ribosomal A-site studied with Brownian dynamics.
作者信息
Długosz Maciej, Antosiewicz Jan M, Trylska Joanna
机构信息
Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Żwirki i Wigury 93, Warsaw 02-089, Poland.
出版信息
J Chem Theory Comput. 2008 Apr;4(4):549-559. doi: 10.1021/ct700210n.
Abstract
Brownian dynamics methodology was applied to simulate the encounter of aminoglycosidic antibiotics with the ribosomal A-site RNA. Studied antibiotics included neamine, neomycin, ribostamycin and paromomycin which differ in chemical structure, the number of pseudo-sugar rings and the net charge. The influence of structural, electrostatic and hydrodynamic properties of antibiotics on the kinetics of their association with the ribosomal A-site was analyzed. The computed diffusion limited rates of association are of the order of 10(10)[Formula: see text] and they weakly depend on ionic strength. Prior to binding antibiotics often slide along the RNA groove with the time scale of approximately 10 ns per base pair in case of neamine. We observed that upon forming the encounter complex aminoglycosides displace from the binding pocket up to two Mg(2+) ions.
摘要
采用布朗动力学方法模拟氨基糖苷类抗生素与核糖体A位点RNA的相遇过程。所研究的抗生素包括新霉素、新霉素、核糖霉素和巴龙霉素，它们在化学结构、假糖环数量和净电荷方面存在差异。分析了抗生素的结构、静电和流体动力学性质对其与核糖体A位点结合动力学的影响。计算得到的扩散限制结合速率约为10(10)[公式：见正文]，且它们对离子强度的依赖性较弱。在结合之前，抗生素通常会沿着RNA凹槽滑动，如新霉素的情况下，每对碱基的时间尺度约为10纳秒。我们观察到，在形成相遇复合物时，氨基糖苷类抗生素会从结合口袋中取代多达两个Mg(2+)离子。
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