214th American Chemical Society Meeting, Las Vegas, September 7-11, 1997

Molecular Dynamics of Peptide Folding at Aqueous Interfaces

Andrew Pohorille and Christophe Chipot

NASA-Ames Research Center Department of Pharmaceutical Chemistry, University of California, San Francisco

Even though most monomeric peptides are disordered in water they can adopt sequence-dependent, ordered structures, such as -helices, at aqueous interfaces. This property is relevant to cellular signaling, membrane fusion, and the action of toxins and antibiotics. The mechanism of folding nonpolar peptides at the water-hexane interface was studied in the example of an 11-mer of poly-L-leucine. Initially placed as a random coil on the water side of the interface, the peptide folded into an -helix in 36 ns. Simultaneously, the peptide translocated into the hexane side of the interface. Folding was not sequential and involved a 3-helix as an intermediate. The folded peptide was either parallel to the interface or had its C-terminus exposed to water. An 11-mer, LQQLLQQLLQL, composed of leucine (L) and glutamine (G), was taken as a model amphiphilic peptide. It rapidly adopted an amphiphilic, disordered structure at the interface. Further folding proceeded through a series of amphiphilic intermediates.