Alpha-Helix Formation Studied with Pressure Perturbation Calorimetry (2008)

Undergraduates: Naima Sharaf, Naima Sharaf Kristin Fuchs, Ashutosh Tripathy

Faculty Advisor: Gary Pielak
Department: Chemistry

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Pressure perturbation calorimetry (PPC) is a relatively unexplored technique that quantifies the temperature dependence of a solute’s thermal expansion coefficient. PPC data provides information about solute-solvent interactions. To investigate the formation of an a-helix in solution, PPC was used to characterize helix-solvent and random coil-solvent interactions. Helix and random coil models were obtained by using two peptides, Ac-DKDGYISAAE-NH2 (P12) and Ac-DKDGDGYISAAEAAAQ-NH2 (P16) which contain the same sequence for the first twelve amino acids, while the last 4 residues of P16 form a La3+ inducible a-helix. When La3+ is absent, both peptides are primarily random coils, with a small amount of residual helix. The amount of this residual helix decreases with increasing temperature. Circular dichroism spectropolarimetry was used to determine the temperature dependence of the helix content, both in the presence and absence of La3+. This data was used to correct the raw PPC data. PPC data suggests that the helix-solvent interactions are hydrophobic, while random coil-solvent interactions are slightly less hydrophobic. Therefore, the dominant solvent-solute interactions are not caused by a dramatic change accessible solvent area (ASA), but are instead due to formation of a dipole upon helix formation. This result is consistent with the accepted view that helix formation does not result in a large change in ASA.