Light-triggered beta-hairpin folding and unfolding.

Area of Science:

• Biophysics
• Computational Chemistry
• Spectroscopy

Background:

• Light-responsive peptides offer controllable molecular switches.
• Understanding peptide dynamics is crucial for biomolecular engineering.

Purpose of the Study:

• To investigate the ultrafast structural dynamics of a light-switchable peptide.
• To elucidate the energy landscape governing peptide folding and unfolding transitions.

Main Methods:

• Utilized ultrashort laser pulses to trigger peptide structural changes.
• Employed mid-infrared (mid-IR) probing for real-time structural monitoring.
• Applied instantaneous normal mode analysis with a hybrid DFT/MM Hamiltonian for theoretical interpretation.

Main Results:

• Observed rapid transformation from beta-hairpin to unfolded hydrophobic cluster within nanoseconds upon illumination.
• Identified a reaction pathway with minimal free-energy barriers for unfolding.
• Determined that the reverse folding process is significantly slower, occurring on the microsecond timescale.

Conclusions:

• Peptide unfolding is a barrier-less process on the nanosecond timescale.
• Peptide folding is a kinetically controlled process requiring extensive conformational searching on the microsecond timescale.
• The study provides insights into the fundamental mechanisms of protein dynamics and light-induced molecular switching.