Among the simplest electrobiochemical pathways to characterize experimentally is a series of electron transfer reactions that provide the mechanism for dehydrogenation of methylamine. We describe a computational investigation of the chemical reaction mechanism for the enzyme activity of methylamine dehydrogenase in converting methylamine to ammonia and formaldehyde, focusing on the activity of the cofactor tryptophan tryptophylquinone (TTQ). The free energies, reaction rate constants, and related effects of temperature, pH, and isotopic substitution are being computed for comparison against experimental observations. Electronic structure calculations are carried out by density functional methods shown to be effective in the study of simpler chemical systems involving the dynamics of conjugated pi-electron systems. The reaction

energies of several reaction steps have been mapped along selected reaction coordinates, and additional reaction steps are currently being probed to determine the minimum energy path. The COSMO-RS model will then be applied to account for the considerable solvent effects in ion-mediated reaction dynamics, and will allow determination of the influence of pH on the reaction system.