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 (CH(2))(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.