Structure and dynamics of small peptides at aqueous interfaces a multi-nanosecond molecular dynamics study

Abstract

The dynamical and the mechanistic aspects of peptide folding have been examined at aqueous interfaces in a series of large-scale molecular dynamics computer simulations. The conformational equilibria of the heptapeptide, made of the nonpolar l-leucine and the polar l-glutamine amino acids, having a sequence of hydrophobic periodicity of 3.6, and initially organized as an α-helix or a β-strand, were investigated at the water liquid-vapor interface. The behavior of the Ac- and NHMe-blocked undecamer of poly- l-leucine in the water-hexane system, initially located on the water side of the interface in a random coil conformation, was examined over 34 ns. For comparison, conformational preferences of the prototypical terminally blocked l-leucine, l-glutamine and l-alanine single amino acids, as well as their corresponding dimers, were studied. These multinanosecond simulations shed light on three important properties of small peptides at aqueous interfaces. First, oligopeptides containing both polar and nonpolar amino acids show a clear tendency to accumulate at the interface. Second, aqueous interfaces, unlike water, appear to mediate folding, so that peptides built of leucine and glutamine readily adopt amphiphilic conformations. Third, fully nonpolar peptides become inserted into a nonpolar phase by concurrent partitioning and folding into a helical structure. A complete folding process was observed during the simulations.