Interactions between membrane proteins (MPs)/antimicrobial peptides (AMPs) and lipids play important roles in the creation and function of membrane transport events like ion channels, defects, etc. Energetics based on these interactions have been found to explain various aspects of
general drug effects on cell membranes. We have used various membrane active agents (MAAs) such as peptides, chemotherapy drugs, amphipathic molecules, amphiphiles, etc. to observe the complexes created between them and lipids in bilayers that often serve as membrane transport events in order
to better understand the underlying mechanism(s). We find that the structures and functions of MAAs-lipids complexes are very specific to the respective MAAs. However, the underlying mechanisms originating from some common types of interactions are found to depend on physical properties of
both MAAs and lipids. Specifically, the stability and functions of MAAs-lipid complexes depend primarily on the electrostatic energy coupling between MAAs and lipids. The mechanical energy coupling between MAAs and lipids, depending mainly on the bilayer elastic profiles, contributes just
secondary effects into the stability and functions of the complexes. Both of these electrostatic and mechanical energetic couplings emerge from a unique interaction energy expression appearing from screened Coulomb interaction treatment between MAAs and lipids, mainly depending on the localized
charge profiles and on other physical properties of both MAAs and lipids. This review will address the functions and underlying molecular mechanisms of membrane transport events, membrane effects of general drugs, etc. and thus will open up avenues leading to novel drug discovery.
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