Current Topics Impact of Enzyme Motion on Activity †

ABSTRACT: Experimental and theoretical data imply that enzyme motion plays an important role in enzymatic reactions. Enzyme motion can influence both the activation free energy barrier and the degree of barrier recrossing. A hybrid theoretical approach has been developed for the investigation of the relation between enzyme motion and activity. This approach includes both electronic and nuclear quantum effects. It distinguishes between thermally averaged promoting motions that influence the activation free energy barrier and dynamical motions that influence the barrier recrossings. Applications to hydride transfer in liver alcohol dehydrogenase and dihydrofolate reductase resulted in the identification and characterization of important enzyme motions. These applications have also led to the proposal of a network of coupled promoting motions in enzymatic reactions. These concepts have important implications for protein engineering and drug design. The relation between enzyme motion and activity has been probed with a variety of experimental techniques. Highresolution crystal structures for intermediates along enzymatic reaction pathways have provided evidence of substantial conformational changes (1). NMR experiments have been used to identify dynamic regions both in the active sites and far from the active sites of enzymes (2-4). These dynamic regions have been found to change along the enzymatic reaction pathway. In addition, kinetic measurements on mutant enzymes have shown significant changes in the catalytic rate for mutations both in the active site and far from the active site (5-7). Furthermore, double mutations exhibit nonadditive effects (8, 9) [i.e., the effect of the double mutation is greater than the sum of the effects of the corresponding single mutations (10)], suggesting coupling between distal regions of the enzyme. These experimental observations imply that enzyme motion is a significant factor in enzymatic reactions. Theoretical simulations of enzymatic reactions have provided further insight into the role of enzyme motion For clarification, we define the terminology used in this review. The term "dynamics" is reserved for motions that influence the transmission coefficient (i.e., the barrier recrossings)

QM/MM Modeling of Vibrational Polariton Induced Energy Transfer and Chemical Dynamics

Vibrational strong coupling (VSC) provides a novel means to modify chemical reactions and energy transfer pathways. To efficiently model chemical dynamics under VSC in the collective regime, herein a hybrid quantum mechanical/molecular mechanical (QM/MM) cavity molecular dynamics (CavMD) scheme is developed and applied to an experimentally studied chemical system. This approach can achieve linear scaling with respect to the number of molecules for a dilute solution under VSC by assuming that each QM solute molecule is surrounded by an independent MM solvent bath. Application of this approach to a dilute solution of Fe(CO)$_5$ in n-dodecane under VSC demonstrates polariton dephasing to the dark modes and polariton-enhanced molecular nonlinear absorption. These simulations predict that strongly exciting the lower polariton may provide an energy transfer pathway that selectively excites the equatorial CO vibrations rather than the axial CO vibrations. Moreover, these simulations also directly probe the cavity effect on the dynamics of the Fe(CO)$_5$ Berry pseudorotation reaction for comparison to recent two-dimensional infrared spectroscopy experiments. This theoretical approach is applicable to a wide range of other polaritonic systems and provides a tool for exploring the use of VSC for selective infrared photochemistry.Comment: 19 pages, 5 figures in the main tex

Improvement of the internal consistency in trajectory surface hopping

This paper addresses the issue of internal consistency in the molecular dynamics with quantum transitions (MDQT) surface hopping method. The MDQT method is based on Tully's fewest switches algorithm, which is designed to ensure that the fraction of trajectories on each surface is equivalent to the corresponding average quantum probability determined by coherent propagation of the quantum amplitudes. For many systems, however, this internal consistency is not maintained. Two reasons for this discrepancy are the existence of classically forbidden transitions and the divergence of the independent trajectories. This paper presents a modified MDQT method that improves the internal consistency. The classically forbidden switches are eliminated by utilizing modified velocities for the integration of the quantum amplitudes, and the difficulties due to divergent trajectories are alleviated by removing the coherence of the quantum amplitudes when each trajectory leaves a nonadiabatic coupling region. The standard and modified MDQT methods are compared to fully quantum calculations for a classic model for ultrafast electronic relaxation (i.e., a two-state threemode model of the conically intersecting S 1 and S 2 excited states of pyrazine). The standard MDQT calculations exhibit significant discrepancies between the fraction of trajectories in each state and the corresponding average quantum probability. The modified MDQT method leads to remarkable internal consistency for this model system

Nonadiabatic dynamics for processes involving multiple avoided curve crossings: Double proton transfer and proton-coupled electron transfer reactions

The extension of the surface hopping method ''molecular dynamics with quantum transitions'' ͑MDQT͒ to double proton transfer and proton-coupled electron transfer reactions is tested by comparison to fully quantum dynamical calculations for simple model systems. These model systems each include four potential energy surfaces and three or four avoided curve crossings. The agreement between the MDQT and fully quantum dynamical calculations provides validation for the application of MDQT to these biologically important processes. © 1997 American Institute of Physics. ͓S0021-9606͑97͒50745-8

First-Principles Approach for Coupled Quantum Dynamics of Electrons and Protons in Heterogeneous Systems

The coupled quantum dynamics of electrons and protons is ubiquitous in many dynamical processes involving light-matter interaction, such as solar energy conversion in chemical systems and photosynthesis. A first-principles description of such nuclear-electronic quantum dynamics requires not only the time-dependent treatment of nonequilibrium electron dynamics but also that of quantum protons. Quantum mechanical correlation between electrons and protons adds further complexity to such coupled dynamics. Here we extend real-time nuclear-electronic orbital time-dependent density functional theory (RT-NEO-TDDFT) to periodic systems and perform first-principles simulations of coupled quantum dynamics of electrons and protons in complex heterogeneous systems. The process studied is electronically excited state intramolecular proton transfer of o-hydroxybenzaldehyde in water and at a silicon (111) semiconductor-molecule interface. These simulations illustrate how environments such as hydrogen-bonding water molecules and an extended material surface impact the dynamical process on the atomistic level. Depending on how the molecule is chemisorbed on the surface, excited state electron transfer from the molecule to the semiconductor surface can inhibit ultrafast proton transfer within the molecule. This work elucidates how heterogeneous environments influence the balance between the quantum mechanical proton transfer and excited electron dynamics. The periodic RT-NEO-TDDFT approach is applicable to a wide range of other photoinduced heterogeneous processes

Computational Study of Fluorinated Diglyoxime-Iron Complexes: Tuning the Electrocatalytic Pathways for Hydrogen Evolution

The ability to tune the properties of hydrogen-evolving molecular electrocatalysts is important for developing alternative energy sources. Fluorinated diglyoxime-iron complexes have been shown to evolve hydrogen at moderate overpotentials. Herein two such complexes, [(dAr^FgBF_2)_2Fe(py)_2], denoted A, and [(dAr^Fg_2H-BF_2)Fe(py)_2], denoted B [dAr^Fg = bis(pentafluorophenyl-glyoximato); py = pyridine], are investigated with density functional theory calculations. B differs from A in that one BF_2 bridge is replaced by a proton bridge of the form O–H–O. According to the calculations, the catalytic pathway for A involves two consecutive reduction steps, followed by protonation of an Fe^0 species to generate the active Fe^(II)-hydride species. B is found to proceed via two parallel pathways, where one pathway is similar to that for A, and the additional pathway arises from protonation of the O–H–O bridge, followed by spontaneous reduction to an Fe^0 intermediate and intramolecular proton transfer from the ligand to the metal center or protonation by external acid to form the same active Fe^(II)-hydride species. Simulated cyclic voltammograms (CVs) based on these mechanisms are in qualitative agreement with experimental CVs. The two parallel pathways identified for B arise from an equilibrium between the protonated and unprotonated ligand and result in two catalytic peaks in the CVs. The calculations predict that the relative probabilities for the two pathways, and therefore the relative magnitudes of the catalytic peaks, could be tuned by altering the pK_a of the acid or the substituents on the ligands of the electrocatalyst. The ability to control the catalytic pathways through acid strength or ligand substituents is critical for designing more effective catalysts for energy conversion processes