Theoretical investigation of photoinduced electron transfer in flavodoxin from molecular dynamics simulation data

Abstract

Photoinduced electron transfer (PET) in enzyme plays significant roles in many biological processes. In this work, PET in flavodoxin from Desulfobivrio vulgaris, strain Miyazaki F (FD-DvMF) and from Helicobacter pylori (FD-HP), in which both bind one molecule of FMN as a cofactor, were studied using several molecular modeling techniques. Four FD-DvMF structures (wild type, W59F, Y97F and W59F-Y97F) were generated by homology modeling while the wild type structure of FD-HP was taken from the protein data bank. Molecular dynamics (MD) simulations of all five systems were carried out to investigate FMN-enzyme binding interaction as well as their dynamic properties. The decomposition free energy calculations indicate that the 10-loop region has the highest contribution to the binding, which is due to the H-bonding between phosphate subsite and amino acids. Ensemble of conformations obtained from the MD simulations of the five systems was supplied into the Kakitani and Mataga theory to analyze the PET mechanisms by fitting with experimental fluorescence quenching data. It was found that the mean electron transfer rate from Trp59 to excited Iso (Iso*) in the wild type was the fastest among the four FD-DvMF and it is from Tyr92 to Iso* for the FD-HP. In addition, the net electrostatic energy and the standard free energy change of the reaction are the most influential factors for the ultrafast electron transfer rate. The charge transfer (CT) was further studied by using quantum chemistry method. The calculations reveal that the state is the locally excited state while the S₂ state shows CT state characteristic.