Lopez Carlos F, Nielsen Steven O, Srinivas Goundla, Degrado William F, Klein Michael L
Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104-6323, USA.
J Chem Theory Comput. 2006 May;2(3):649-655. doi: 10.1021/ct050298p.
Knowledge of the mechanism of action of antimicrobial agents is crucial for the development of new compounds to combat microbial pathogens. To this end, computational studies on the interaction of known membrane-active antimicrobial polymers with phospholipid bilayers reveal spontaneous membrane insertion and cooperative action at low and high concentrations, respectively. In late-stage attack, antimicrobials cross the membrane core and occasionally align to provide a stepping-stone pathway for water permeation; this suggests a possible new mode of action that does not depend on pore formation for transport to and across the inner leaflet. The computations rationalize the observed activity of a new class of antimicrobial compounds.
了解抗菌剂的作用机制对于开发对抗微生物病原体的新化合物至关重要。为此，对已知的膜活性抗菌聚合物与磷脂双层相互作用的计算研究分别揭示了在低浓度和高浓度下的自发膜插入和协同作用。在后期攻击中，抗菌剂穿过膜核心并偶尔排列以提供水渗透的垫脚石途径；这表明了一种可能的新作用模式，该模式不依赖于形成孔来运输到内膜并穿过内膜。这些计算使一类新型抗菌化合物的观察到的活性合理化。
