THE CONFORMATIONS OF PROLINE-LINKED DONOR-ACCEPTOR SYSTEMS

We have carried out a simulation study of the stable conformations of Pro-Pro peptides in solution, and of Pro(n) peptides (where n = 1-4) in a dielectric continuum model, to explain the observed electron-transfer rates in proline-linked donor-acceptor systems studied by Isied and Vassilian.1 They found that the rate of electron transfer in proline-linked donor-acceptor systems decreases by the expected amount for Pro2 versus Pro1, but for Pro3 and Pro4 the rate increases, with Pro4 having the fastest transfer rate of the peptides studied. This finding suggests that conformational flexibility in the longer peptides enables the donor and acceptor to reach short transfer distances, resulting in the faster transfer rate. We have performed conformational free energy simulations to determine the free energy barriers for transitions of the backbone degrees of freedom of Pro-Pro peptides in solution. From the stable structures found we have carried out simulations of the Pro1-to-Pro4-linked donor-acceptor systems to determine the structural changes that best explain the observed trend in the electron-transfer rates. We found that the proline secondary structures poly(Pro)I and poly(Pro)II cannot explain the trend in transfer rates and that, instead, transitions of the psi backbone dihedral from an extended to an a conformation can give short enough transfer distances to explain the experimental rates. Our analysis suggests that transitions of the backbone psi dihedral angle represent a significant mechanism for conformational change in proline peptides.