HYDROPHILIC SURFACE MAPS OF CHANNEL-FORMING PEPTIDES - ANALYSIS OF AMPHIPATHIC HELICES

Ion channels may be formed by bundles of amphipathic alpha-helices ali gned parallel to one another and spanning a lipid bilayer membrane, wi th the hydrophilic faces of the helices lining a central pore. In orde r to provide insight into the packing of such helices in bundles, a me thod has been developed to evalute hydrophilic surface maps of amphipa thic alpha-helices and to display these surfaces in a readily interpre table form. The procedure is based upon empirical energy calculations of interactions of a water molecule with an amphipathic alpha-helix. T he method has been applied to three channel-forming peptides: Staphylo coccal delta-toxin; alamethicin; and a synthetic leucine- and serine-c ontaining peptide. Particular emphasis is placed upon the effects of s idechain conformational flexibility on hydrophilic surface maps. A fam ily of models of the delta-toxin helix is generated by a simulated ann ealing procedure. The results of hydrophilic surface map analyses prov ide more exact definition of the centre of the hydrophilic face of amp hipathic helices, and of the variation of the position of the centre i n response to changes in sidechain conformation. This information is u sed to define families of preliminary models for a given ion channel, as is illustrated for delta-toxin.