Dynamics and Mechanism of Membrane-Induced Folding of a Small Beta-Hairpin

Abstract

A complementary approach of experiments and computation were used to characterize the dynamics and mechanism of peptide folding and insertion into the membrane. SVS-1, an 18-residue anti-cancer peptide that is designed to be disordered in solution, but fold into a β-hairpin at an anionic bilayer surface, was used as a model system for protein folding on the membrane. Infrared and fluorescence where used to characterize the folding of the peptide in the membrane. Laser induced temperature-jumps (T-jump) were used to initiate the folding reaction. Computational models of tryptophan-containing SVS-1 mutants were used to guide the choice of targets for fluorescent studies. Molecular dynamic simulations model the folded and unfolded states at the bilayer surface to estimate timescales of binding, folding and insertion. Simulations were used to interpret and guide future experiments.