Protein-membrane interactions:: Lessons from in silico studies

Membrane and membrane-active peptides and proteins play a crucial role in numerous cell processes.. such as signaling, ion conductance, fusion, and others. Many of them act as highly specific and efficient drugs or drug targets, and, therefore.. attract growing interest for biomedical applications. Because of experimental difficulties with characterization of their spatial structure and mode of membrane binding, essential attention is given now to molecular modeling techniques. During the last years an important progress has been achieved in computer simulations of peptides and proteins with various types (implicit and/or explicit) of theoretical models of membranes. The present work sums up our recent results of molecular dynamics (MD) simulations of binding of several membrane active peptides and proteins to hydrated lipid bilayers and detergent micelles. To check the predictive power of the computational approach, peptides and proteins with diverse folding (alpha-helical and beta-structural), mode of membrane binding.. and biological activities were studied. Among them are cardiotoxins (CTXs) from snake venom and fusogenic peptides. The emphasis is made on structural and/or functional information which may be obtained via molecular modeling. In particular, to address the question about the role of membrane composition in protein-lipid interactions, MD simulations were performed in lipid bilayers differing in length, of acyl chains, chemical nature and/or charge of headgroups. It was shown that the results obtained are in a reasonable agreement with experimental data. Possible relationships between the structural/dynamic properties of proteins in different membrane-mimic media and their biological activities are discussed. The approximations and shortcomings of the theoretical models.. along with their perspectives in design of new membrane active drugs. are outlined. A general conclusion was reached that in silico technologies represent a powerful tool in the field of structural biology of membrane proteins.