Sequential Proton Coupled Electron Transfer (PCET): Dynamics Observed over 8 Orders of Magnitude in Time.

Charge transfer mechanisms lay at the heart of chemistry and biochemistry. Proton coupled electron transfers (PCET) are central in biological processes such as photosynthesis and in the respiratory chain, where they mediate long-range charge transfers. These mechanisms are normally difficult to harness experimentally due to the intrinsic complexity of the associated biological systems. Metal-peptide cations experience both electron and proton transfers upon photoexcitation, proving an amenable model system to study PCET. We report on a time-resolved experiment designed to follow this dual charge transfer kinetics in [HG3W+Ag](+) (H = histidine, G = glycine, W = tryptophan) on time scales ranging from femtoseconds to milliseconds. While electron transfer completes in less than 4 ps, it triggers a proton transfer lasting over hundreds of microseconds. Molecular dynamics simulations show that conformational dynamic plays an important role in slowing down this reaction. This combined experimental and computational approach provides a view of PCET as a single phenomenon despite its very wide time-domain span.

Effect of Single-Point Mutations on Nitric Oxide Rebinding and the Thermodynamic Stability of Myoglobin.

The effect of single amino acid mutations on the rebinding dynamics of nitrogen monoxide (NO) to myoglobin is investigated using reactive molecular dynamics simulations. In particular, mutations of residues surrounding the heme-active site (Leu29, His64, Val68) were considered. Consistent with experiments, all mutations studied here have a significant effect on the kinetics of the NO-rebinding process, which consists of a rapid (several 10 ps) and a slow (100s of ps) time scale. For all modifications considered, the time scales and rebinding fractions agree to within a few percents with results from experiments by adjusting one single, physically meaningful, conformationally averaged quantity: the asymptotic energy separation between the NO-bound (2A) and photodissociated (4A) states. It is furthermore shown that the thermodynamic stability of wild-type versus mutant Mb for the ligand-free and ligand-bound variants of the protein can be described by the same computational model. Therefore, ligand kinetics and thermodynamics are related in a direct fashion akin to Φ-value analysis, which establishes a relationship between protein folding rates and thermal stability of proteins.