Peptide folding dynamics: a time-resolved study from the nanosecond to the microsecond time regime

Area of Science:

• Biochemistry
• Biophysics
• Computational Chemistry

Background:

• Trichogin GA IV is a natural undecapeptide with antimicrobial properties.
• Its structure features constrained alpha-aminoisobutyric acid and a glycine-glycine motif.
• Understanding peptide conformation is crucial for antimicrobial activity and protein folding studies.

Purpose of the Study:

• To investigate the solution conformations and dynamics of trichogin GA IV analogues.
• To correlate structural properties with antimicrobial activity.
• To model early stages of protein hydrophobic collapse.

Main Methods:

• Time-resolved spectroscopies (nanosecond fluorescence, microsecond transient absorption).
• Molecular mechanics calculations.
• Distance-dependent fluorophore-quencher interaction analysis.
• Photophysical experiments varying medium viscosity and polarity.

Main Results:

• Identified populated conformations in solution for peptide analogues.
• Observed a transition from elongated helical structures to compact, folded conformations.
• Demonstrated that these folded structures mimic a helix-turn-helix motif.
• Provided insights into peptide dynamics on nanosecond to microsecond timescales.

Conclusions:

• The studied peptide analogues undergo significant conformational changes in solution.
• These conformational transitions may serve as a model for protein hydrophobic collapse.
• The findings contribute to understanding peptide structure-function relationships and protein folding mechanisms.