Flora Meilleur

Flora Meilleur

Position: Lead Instrument Scientist

Instrument: Laue Diffractometer

Group: Energy and the Environment

Division: Biology and Soft Matter Division

Facility: High Flux Isotope Reactor

Contact: meilleurf@ornl.gov or (865) 576-2779

My primary research interest is in mapping intra- and intermolecular interactions that govern enzyme function within the microenvironment of the catalytic site. Knowledge of local electrostatics, hydrogen-bonding networks and protonation states of titratable catalytic residues is essential for proper thermodynamic modeling and for predicting binding interactions in molecular recognition and catalysis.

Biological catalysts, or enzymes, fluctuate to function. While the prevailing structure based view of enzymes is of a scaffold that precisely positions a few key catalytic residues, the process is intrinsically dynamic and relies upon a series of coordinated chemical and structural changes throughout the reaction cycle. As a result, the microenvironment at and around the active site of the enzyme can fluctuate significantly, altering and perturbing local electrostatics, H-bonding interactions and the pKa of titratable catalytic residues. While small structural changes that result in minor conformations can dominate reactivity in some systems, many enzymes require substantial conformational changes in order to bind, position, process and release their reactants. When these active sites are buried within extended tunnels or clefts, additional questions arise on how local conformational flexibility and chemical environment couple to control binding and release of substrate and product.

I primarily combine atomic structure determination using X-ray and neutron crystallography and molecular dynamics approaches to map relationships between the electrostatic micro-environment of amino-acids, local dynamics and protonation states.

I am also interested in understanding the structural changes that are associated with virus assembly, attachment and infection at cell membranes. We use a suite of structural techniques, including crystallography, small angle neutron scattering (SANS), and reflectometry to model the structural rearrangement undergone by virus particles during the infection process.

More detailed information is available.


Ph. D. in Structural Biology, Université Joseph Fourier & The European Molecular Biology Laboratory, Grenoble, France


Position Held

  • 2004 – 2006 Instrument Scientist, Institut Laue Langevin
  • 2007- Present Joint Assistant Professor of Biochemistry, Oak Ridge National Laboratory & North Carolina State University
  • 2009 – Present: Lead instrument scientist, Oak Ridge National Laboratory & North Carolina State University

Selected Publications

Munshi P., Snell E.H, Van der Woerd M.J., Judge R.A., Myles D.A., Ren Z., Meilleur F. (2014) Hydrogen bonding interaction at the active site of cyclic glucose bound xylose isomerase E186Q mutant. Acta Cryst. D70:414-420

Gruene T., Hahn H.W., Meilleur F., Sheldrick G.M. (2014) Refinement of macomolecular structures against neutron data with SHELXL-2013. J. Appl. Cryst. 47:462-466

Meilleur F., Munshi P., Kovalevsky A., Koritsanszky T., Blessing R., Robertson L., Stoica A.D., Crow L., Myles D.A. (2013) IMAGINE: First Neutron Protein Structure and New capabilities for neutron macromolecular crystallography. Acta Cryst. D69:2157-2160

Myles D.A., Dauvergne F., Blakeley M.P., Meilleur F. (2012) Neutron protein crystallography at ultra- low (<15K) temperatures. J. Appl. Cryst. 45:686-692

Munshi P., Chung S.-L., Weiss K.L., Blakeley M.P., Myles D.A., Meilleur F. (2012) Rapid visualization of hydrogen positions in neutron crystallography structures. Acta Cryst. D68:35-41