Computational Study of Antimicrobial Peptide-lipid Membrane Interactions

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

The objectives of this project are to understand the fundamental mechanism of the interaction between antimicrobial peptides (AMP) and lipid membranes and to understand the basic mechanism of pore formation in lipid membranes by AMPs. To accomplish the first goal, the Principal Investigator (PI) will perform all atom computer simulations in order to calculate the free energy of peptide adsorption and its permeation across the lipid membrane. The microscopically detailed information that will be obtained from simulations will allow the PI to determine the energetic gain upon peptide adsorption and the pathway of peptide permeation across the membrane. The second specific goal of the project will be accomplished by performing simulations on systems containing multiple peptides and a bilayer. The bilayer will contain either one kind of a lipid or will be composed of a mixture of lipids having biological significance. The role of some specific lipids present in the membrane will be carefully considered. For example, the recent experimental study of cholesterol influence on action of AMPs produced controversial results and interpretations. The molecular detailed picture provided by simulations will be extremely useful to resolve these controversies. To understand the molecular architecture of pores in cell membranes, the PI will also perform comparative simulations on systems containing different AMPs. In general, simulations performed by the PI will provide a link between experiment, phenomenological theory and the microscopic details responsible for AMP action in membranes. Broader Impacts Work on the project will provide essential training in the biophysics of membranes for undergraduate and graduate students and postdoctoral fellows. The results from the research will be discussed in the lectures the PI gives in a course on membranes which is taught as a module in the Molecular and Cellular Biophysics program at the University of North Carolina. A less quantitative version of these lectures is given in the Biophysical Society summer course in biophysics for minority students. The objective of this course is to introduce minority students from colleges and universities lacking formal programs in biophysics to the exciting world of mechanistic and structural biology, and the possibility of a career in biophysics. Some of the students from the course also get hands on experience in membrane biophysics by performing research in the PI's laboratory. The PI is also participating in the work of the International Graduate Research Training Group, which includes faculty and students, mainly from Germany and North Carolina. Under the framework of this Group's activities, students from the laboratories in Germany will be able to visit the PI's laboratory and work on the projects related to the study of peptide/membrane interactions, while students from the PI's group will be able to visit Germany.