Membrane permeation is involved in mass and signal transfers between the interior of a cell and its environment and is a fundamental process in almost every biological system. Understanding the interaction between bioorganic molecules and membrane plays an important role in drug development and pathological study. In this presentation, I will present the application of metadynamics combined with our recent developments to investigate the passive permeation of drug molecules. Besides the mass transfer, the passive permeation process is also governed by the hydrophobic/hydrophilic interaction. This research has demonstrated that our method is able to model the complicated permeation process and to predict a very accurate permeability. Further, I will present the study of the interaction between mycolactone and lipid bilayers, which is the exotoxin produced by Mycobacterium ulcerans that act as the key virulence factor behind Buruli ulcer disease. It kills host cells via a myriad of interactions with cytosolic and membrane-bound targets. Although it is thought to passively permeate through host membranes, its interactions with membranes are unclear given its amphiphilic structure. In this work, we characterize membrane permeation and aggregation of this large toxin in atomistic molecular dynamics simulations and find that the exotoxin has a strong affinity for the lipid bilayer. We will also discuss the membrane defects introduced by the present of mycolactone, which might lead to phase behavior change. These findings suggest that lipids play an integral role in the transport and delivery of mycolactone to and within host cells.

Interactions between bioorganic molecules and membrane: Passive permeation, membrane defects, and phase behavior

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.