Conformational Sampling of Influenza Fusion Peptide in Membrane Bilayers as a Function of Termini and Protonation States
|Title||Conformational Sampling of Influenza Fusion Peptide in Membrane Bilayers as a Function of Termini and Protonation States|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Panahi, A, Feig, M|
|Journal||Journal of Physical Chemistry B|
|Type of Article||Journal Article|
Influenza fusion peptide is critical for mediating the fusion of viral and host cell membranes during viral entry. The interaction of monomeric influenza fusion peptide with membranes is studied with replica exchange molecular dynamics simulations using a new implicit membrane model to effectively reach microsecond to millisecond time scales. The conformational sampling of the fusion peptide was studied as a function of different N- and C-termini, including an experimental construct with an additional C-terminal tag, as well as a function of protonation of acidic residues. It is found that the influenza fusion peptide mostly adopts helical structures with a pronounced kink at residues 11−13 with both N-terminal and C-terminal helices oriented mostly parallel to the membrane surface. A charged C-terminus and the presence of a charge C-terminal tag significantly alters the conformational sampling of the fusion peptide and results in more diverse conformational ensembles that include obliquely inserted N-terminal peptide structures. Protonation of acidic residues also affects the conformational sampling, however, based on pKa shift estimates the overall effect of pH = 5 on the conformational sampling of the influenza fusion peptide appears to be only minor.