Enzymatic Catalysis Research at ORNL

Oak Ridge National Laboratory has several projects in the area of enzyme catalysis. These projects are primarily undertaken by the members of UT/ORNL Center for Molecular Biophysics or CMB. CMB currently focuses on the enzymes that catalyze biologically important reactions or have potential impacts on environmental remediation and bioenergy. The goal of these projects is to provide a fundamental, molecular-level description of catalytic processes and determine origin of catalytic effects. The CMB teams try to integrate high-performance computer simulation, neutron scattering and other techniques to harness catalytic powers of enzymes for different purposes or to discover potential ways for inhibition of their activities. A unique feature of the CMB projects is the involvement of and collaboration with a number of leading experimental laboratories. The work on enzymes spans the Biological and Environmental, Computational and Neutron Scattering Directorates at ORNL. Some of the CMB research activities on enzyme catalysis are summarized below.

Environmental remediation:

This project is based on computer simulations and neutron scattering experiments and is undertaken in a close collaboration with the SFA program in Environmental Sciences Division, ORNL as well as experimental laboratories at University of Georgia and University of California-San Francisco. The research on the enzyme catalysis part is focused on MerA and MerB, two key bacterial enzymes that catalyze, respectively, the reduction of Hg(II) to Hg(0) and the degrading of organomercurials through protonolysis. The understanding obtained from this project may have a broad impact on future environmental remediation based on a variety of approaches, including applications of microorganisms and synthetic models at Oak Ridge Reservation and elsewhere.

Bioenergy:

The purpose of this project is to carry out computational dynamics simulations of a number enzymes and enzyme families to gain insight into the molecular mechanisms of biomass deconstruction, as one of the important goals of BioEnergy Science Center. The tasks of this project include investigating synergistic actions of enzyme complexes on cellulose and understanding recalcitrance of cellulose to hydrolysis. The results will help to explore the natural diversity of cellulolytic enzyme systems and predict the outcomes of manipulations of enzymes in the development of cost effective strategies of deconstructing cellulosic biomass.

Catalytic mechanisms of enzymes:

There are several other projects in the area of enzyme catalysis currently under investigation by the members of CMB. The key purpose of these projects is to understand mechanisms of enzymes that catalyze some biologically important reactions. One system that is of considerable interest is molecular motor myosin, and important insights have already been obtained concerning the mechanism of ATP hydrolysis in the conversion of chemical energy into mechanical work. Another project is to investigate specificities and mechanisms of histone-modifying enzymes in their writing of epigenetic marks.