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A Perspective on Enzyme Catalysis
A case study for the enzyme dihydrofolate reductase provides evidence for coupled networks of predominantly conserved residues that influence the protein structure and motion that have important implications for the origin and evolution of enzymes, as well as for protein engineering. Expand
Network of coupled promoting motions in enzyme catalysis
A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized, which has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site. Expand
Proton transfer in solution: Molecular dynamics with quantum transitions
We apply ‘‘molecular dynamics with quantum transitions’’ (MDQT), a surface‐hopping method previously used only for electronic transitions, to proton transfer in solution, where the quantum particleExpand
Relating protein motion to catalysis.
This review examines the linkage between protein conformational motions and enzyme catalysis in the context of two enzymes that catalyze hydride transfer, namely dihydrofolate reductase and liver alcohol dehydrogenase. Expand
Free-energy landscape of enzyme catalysis.
Experimental and theoretical evidence is presented to support the concept that enzyme mechanisms should be viewed as "catalytic networks" with multiple conformations that occur serially and in parallel in the mechanism. Expand
Nuclear Quantum Effects and Enzyme Dynamics in Dihydrofolate Reductase Catalysis
Mixed quantum/classical molecular dynamics simulations of the hydride transfer reaction catalyzed by dihydrofolate reductase are presented. The nuclear quantum effects such as zero point energy andExpand
Flexibility, diversity, and cooperativity: pillars of enzyme catalysis.
A general mechanism is presented for enzyme catalysis that includes multiple intermediates and a complex, multidimensional standard free energy surface and protein flexibility, diverse protein conformations, and cooperative conformational changes are important features of this model. Expand
Computational Studies of the Mechanism for Proton and Hydride Transfer in Liver Alcohol Dehydrogenase
In this paper we present computational studies directed at elucidating the mechanism of the oxidation of benzyl alcohol by liver alcohol dehydrogenase (LADH). This enzyme reaction involves a hydrideExpand
Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans
The data presented here provide a glimpse into the evolutionary trajectory of functional DHFR through its protein sequence space that lead to the diverged binding and catalytic properties of the E. coli and human enzymes. Expand
Proton-coupled electron transfer in soybean lipoxygenase.
The proton donor-acceptor vibrational motion plays a vital role in decreasing the dominant donor- acceptor distance relative to its equilibrium value to facilitate the proton-coupled electron transfer reaction. Expand