STABILIZATION OF HELICAL PEPTIDES BY MIXED SPACED SALT BRIDGES

Whether or not surface salt bridges have a strong stabilizing effect o n the native structure in proteins remains uncertain. Previous studies of model peptides have shown that salt bridges spaced at i,i+4 along the chain are more stabilizing than those spaced at i,i+3, with a pref erence for the order acid-base rather than base-acid from N to C termi nus. An analysis of the effect of spacing the ion pairs in short helic al peptides is presented, in which acidic and basic side chains spaced two or three residues apart alternate along the chain. The mixed spac ing proves to be stabilizing relative to pure spacings. A control pept ide in which salt bridges were spaced uniformly three residues apart p roved to form a P-sheet structure rather than cc-helix. This is due to formation of a silk-like apolar face consisting of alanine side chain s; the mesoscopic structure formed by these sheets can be imaged by sc anning microscopy.