Conformational study of the pentadecapeptide 2F10 by circular dichroism, IR spectroscopy and molecular mechanics

Abstract

The conformational profile of the pentadecapeptide of sequenceAVYYCTRGYHGSSLY, capable of mimicking the group-specific ‘a’ determinant of human hepatitis B surface antigen at both the B- and T-cell level, was assessed using the combined informationprovided by circular dichroism (CD) studies, IR spectroscopy and molecular mechanics. Specifically, the CD spectra of the peptide was recorded in various environments including an aqueous buffer, trifluoroethanol, hexafluoroisopropanol and inmicellar solutions of sodium dodecylsulfate in order to analyzeits conformational profile. Analysis of the results suggests the strong tendency of the peptide to adopt β structures in the different structuring media. Furthermore, the IR spectrumof the peptide recorded in DMSO shows absorptions compatible with a β sheet structure. Finally, molecular mechanics calculations using an iterative simulated annealing protocol to sample the conformational space, supplemented by a moleculardynamics simulation in water, suggest as the most important peptide secondary structure feature the adoption of a hairpinconformation. Accordingly, the combined information provided by the different techniques used in the present work, consistently suggest that the peptide 2F10 exhibits a tendencyto adopt a hairpin conformation in solution.