Relationship between conformational dynamics and electron transfer in a desolvated peptide. Part I. Structures

Area of Science:

• Computational chemistry
• Biophysics
• Spectroscopy

Background:

• Understanding peptide structure-function relationships is crucial in biophysics.
• Fluorescence quenching is a key technique for studying molecular interactions.
• Gas-phase investigations provide a simplified yet fundamental view of molecular behavior.

Purpose of the Study:

• To computationally model the structure, dynamics, and energetics of the DyeX-(Pro)(4)-Arg(+)-Trp peptide.
• To establish a numerical framework for interpreting gas-phase fluorescence quenching data.
• To elucidate the mechanisms driving fluorescence quenching in this derivatized peptide.

Main Methods:

• Molecular dynamics (MD) simulations using the AMOEBA force field across a temperature range (150–500 K).
• Ab initio calculations to derive force field parameters for the BODIPY-based dye.
• Energy decomposition analysis at classical and quantum mechanical levels.

Main Results:

• Strong electrostatic, polarization, and dispersion interactions significantly influence the peptide's conformation.
• Hydrogen bonds between the dye linker and tryptophan side chain are identified.
• Analysis reveals stacking conformations between the dye and tryptophan indole, facilitating electron transfer.

Conclusions:

• Electron transfer from tryptophan to the dye is the primary mechanism for fluorescence quenching.
• The rigid polyproline segment plays a role in enabling favorable stacking conformations.
• Computational modeling provides a robust framework for interpreting experimental fluorescence data.