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

摘要

The dynamical and the mechanistic tispects of peptide folding have been examined at aqueous interfaces in a series of large-scale molecular dynamics computer simulations. The c.onfomiaiional equilibria of the heptapeptide, made of the nonpoiar l-leucine and the polar L-glutamine aniino acids, having a sequence of hydrophobia periodicity of 3.6, and initially organized as an a-helix or a 0-strund, were, investigated at the water liquid-vapor interface. The behavior of the Ac- and NI-IMe-blocked undecumer of poly-L-leticino in the watcr-hcxane system, initially located on the water side of the interface in a random coil conformation, was examined over 34 us. For comparison, conl'ormational preferences of (he prototypical terminally blocked l-leucinc, t.-glutamine and i.-alaninc single amino acids, as well as their corresponding dimers, were studied. These multi-nanosecond simulations shed light on three important properties of small peptides at aqueous interfaces. First, pligopeptides containing both polar and nonpoiar 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 leuciiie and glutamine readily adopt amphiphilic conformations. Third, fully nonpoiar peptides become inserted into a nonpoiar phase by concurrent partitioning and folding into a helical structure. A complete folding process was observed during the simulations.