Christophe Chipot

Concentrations of anesthetics across the water-membrane interface; the Meyer-Overton hypothesis revisited

The free energies of transferring a variety of anesthetic and nonanesthetic compounds across water-oil and water-membrane interfaces were obtained using computer simulations. Anesthetics exhibit greatly enhanced concentrations at these interfaces, compared to nonanesthetics. The substitution of the interfacial solubilites of the anesthetics for their bulk lipid solubilities in the Meyer-Overton relation, was found to give a better correlation, indicating that the potency of an anesthetic is directly proportional to its solubility at the interface.

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.

Structure and functions of simple peptides at membrane-water interfaces

Even the simplest protocell must have had the capability to catalyze the chemical reactions needed for its survival and growth, and to communicate with its environment. One group of potential early catalysts and signalling molecules were peptides possible precursors of contemporary enzymes and receptors. Unfortunately, short peptides typically do not exhibit any secondary structure in an aqueous solution and, therefore, do not appear to be suitable for the desired cellular functions. There is, however, a growing body of evidence that peptides, which are disordered in water, acquire an amphiphilic secondary structure at water-air, water-oil or water-membrane interfaces, providing that they have a proper sequence of polar and nonpolar residues. Similarly, hydrophobic peptides can readily organize into a-helices inside a nonpolar phase (e.g. lipid bilayer). The specific identity of the residues is of lesser importance, which is a desirable property in the absence of information molecules.