Noncovalent interactions between unsolvated peptides

The conformations of the unsolvated dimers and trimers produced by electrospraying mixtures of polyalanine-based peptides have been examined using ion mobility measurements in conjunction with molecular dynamics simulations. These multimers can provide models for how the secondary structure associates into the. motifs that makeup the tertiary structure domains of proteins. Mixtures of helix-forming monomers (Ac-A(14)K and Ac-A(15)K and Ac-(GA)(7)K and Ac-A(GA)(7)K; Ac = acetyl, G = glycine, A = alanine, and K = lysine) yield V-shaped helical dimers where the C termini are tethered together by the protonated lysine side chain from one peptide interacting with the C terminus of the other (exchanged lysines). Trimers from the Ac(GA)(7)K and Ac-A(GA)(7)K mixture adopt a pinwheel arrangement of helices with all three C termini tethered together by exchanged lysines. Trimers are much less abundant for the Ac-A(14)K and Ac-A(15)K mixture. The V-shaped dimer and pinwheel trimer arrangement leads to a cooperative electrostatic stabilization of the helices through the interaction of the combined charge with the helix dipoles. Mixtures of globule-forming monomers (Ac-K(GA)(7) and Ac-KA(GA)(7)) form predominantly globular multimers. In some conformations, however, the helical state is stabilized by interactions with the local environment. Examples include the antiparallel arrangement of helices that is present as a minor component for the Ac-K(GA)(7).Ac-KA(GA)(7)+2H(+) dimer and dominant for the Ac-KA(14).Ac-KA(15)+2H(+) dimer, as well as conformations with one or more helices which occur for the trimers from the Ac-K(GA)(7) and Ac-KA(GA)(7) mixture.