1.D.14 The Synthetic Leu/Ser Amphipathic Channel-forming Peptide (L/S-SCP) Family A man-made, synthetic, 21-amino acid peptide containing no formal charges, (LSLLLSL)3, forms proton-selective channels. A similar peptide, (LSSLLSL)3, forms cation-selective channels that conduct protons approximately four times faster than any other cation. Energy minimization models of these channels suggest that (LSLLLSL)3 assembles into trimers or tetramers that contain only a few waters, whereas (LSSLLSL)3 assembles into hexamers or larger aggregates that contain a continuous row of waters. Molecular dynamics simulations indicate that the waters in (LSLLLSL)3 are immobile, whereas those in (LSSLLSL)3 are mobile, although less so than in bulk solution. Long-chain polyamino acids (polyleucine, polyalanine) incorporated into lipid bilayers increased the proton permeability severalfold but did not form discrete channel-like openings. This behavior may reflect induction of a transient leak (between peptide and lipid) rather than the formation of channels.