PG-1 Orientation in Lipid Bilayers: Insights from Molecular Dynamics Simulations and Calculations of Potentials of Mean Force as a Function of Its Tilt Angle

Abstract

Antimicrobial peptides, the so-called host defense peptides (usually 12 to 50 amino acids long), exist in all living organisms and play a key role in host defense and innate immune response. Protegrin-1 (PG-1) is one of such peptides and has the β-hairpin conformations in aqueous solution and membrane environments because of inter-strand disulfide bonds. The oligomer states of PG-1 largely depend on membrane types. PG-1 inserts spontaneously and exists as a monomer in a DLPC membrane. In POPC, the minimum structural unit of PG-1 appears to be a dimer that exists in the membrane. To investigate the PG-1 orientation in lipid bilayers, we have performed comparative molecular dynamics simulations of PG-1 monomer in DLPC and POPC membranes. We have also calculated the potentials of mean force (PMF) of PG-1 monomer (with two different rotation angles) in DLPC and POPC membranes as a function of its tilt angle using the β-hairpin restraint potential that we have recently developed. In this work, we will present the simulation results and the calculated PMFs, along with the comparison of calculated solid-state NMR properties with available experimental data.