The structures of dipeptides, peptide oligomers, alanine rich helices, beta-hairpins, turns and other peptides will be examined at equilibrium and after temperature jumps using two dimensional infrared spectroscopy (2D IR) on the amide-I, II and the N-H modes of peptides. Isotopic labels of 13C, 18O, edited into the peptide structures at selected locations will enhance the spatial resolution. The coupling amongst groups of amide or N-H units and between amide and N-H units will track the kinetics of conformational changes in peptides, helices, beta-turns and models of secondary structure, providing a chemical bond scale perspective on the changes. The equilibrium structure fluctuations of acylproline, proline peptides forming type II beta-turn conformations, peptodimimetics, dialanine peptides, tri and tetra-L-alanine peptides, cyclic decapeptides and linear hexapeptides that form type VI turns will be examined. The vibrational relaxation within, and vibrational energy transfer between spatially separated units of peptides, the frequency fluctuations and the cross correlations between the amide and N-H vibrators will be measured by 2D IR. A bond scale description of rapidly interchanging equilibrium conformations will be obtained from angular, distance and time dependent parameters. The correlations between the structural fluctuations occurring at different spatial locations will be elucidated, clarifying the relations between solvent interactions at different sites in the peptides and providing tests of molecular dynamics simulations of the frictional effects controlling barrier crossing processes on the peptide energy landscape. A residue-by-residue description of the mechanisms of the assembly into secondary structure and disassembly of model helix forming peptides and beta-structures, the kinetics of formation of hydrogen bonds, and the dynamical role of the end residues in turns, and the bond level sequence of events in the formation of alanine rich alpha-helices, beta- hairpins and beta-hairpin mimics will be studied with heat and cold denatured peptides. Systematic isotopic editing (13C and 18O) will ensure that 2D IR exposes the steps in assembly processes.
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