Lipid-mediated adaptation of proteins and peptides in cell membranes

Abstract

The paper overviews the results of computational studies of the molecular mechanisms underlying the adaptation of model cell membranes taking place during their interaction with proteins and peptides. We discuss changes in the structural and dynamic parameters of the water–lipid environment, the hydrophobic/hydrophilic organization of the lipid bilayer surface (the so-called “mosaicity”), etc. Taken together, these effects are called the “membrane response” (MR) and constitute the most important ability of the cell membranes to respond specifically and consistently to the incorporation of extraneous agents, primarily proteins and peptides, and their subsequent functioning. The results of the authors’ long-term research in the field of molecular modeling of MR processes with various spatial and temporal characteristics are described, from the effects of binding of individual lipid molecules to proteins to changes in the integral macroscopic parameters of membranes. The bulk of the results were obtained using the “dynamic molecular portrait” approach developed by the authors. The biological role of the observed phenomena and potential ways of rationally designing artificial membrane systems with specified MR characteristics are discussed. This, in turn, is important for targeted changes in the activity profile of proteins and peptides exerting action on biomembranes, not least as promising pharmacological agents.