Relationship between Conformational Dynamics and Electron Transfer in a Desolvated Peptide. Part I. Structures

The structures, dynamics and energetics of the protonated,
derivatized
peptide DyeX-(Pro)4-Arg+-Trp, where “Dye”
stands for the BODIPY analogue of tetramethylrhodamine and X is a
(CH2)5 linker, have been investigated using
a combination of modeling approaches in order to provide a numerical
framework to the interpretation of fluorescence quenching data in
the gas phase. Molecular dynamics (MD) calculations using the new
generation AMOEBA force field were carried out using a representative
set of conformations, at eight temperatures ranging from 150 to 500
K. Force field parameters were derived from ab initio calculations
for the Dye. Strong electrostatic, polarization and dispersion interactions
combine to shape this charged peptide. These effects arise in particular
from the electric field generated by the charge of the protonated
arginine and from several hydrogen bonds that can be established between
the Dye linker and the terminal Trp. This conclusion is based on both
the analysis of all structures generated in the MD simulations and
on an energy decomposition analysis at classical and quantum mechanical
levels. Structural analysis of the simulations at the different temperatures
reveals that the relatively rigid polyproline segment allows for the
Dye and Trp indole side chain to adopt stacking conformations favorable
to electron transfer, yielding support to a model in which it is electron
transfer from tryptophan to the dye that drives fluorescence quenching.