March 2022 Spotlight
Dr. Mark White
My major
interests include developing the tools of Structural Biology, the
pursuit of novel macromolecular structures and complexes, and their
functional analysis. I employ single crystal x-ray crystallography and
solution macromolecular small angle x-ray scattering (BioSAXS) to
determine the structure and function of macromolecules, their complexes,
and inhibitors. In varied structural collaborations I have studied: a
number of flavivirus proteins, the DNA packaging motor assembly used by
Phage, the assembly of amyloid and self-assembling nanoparticle fibrils,
structural changes to the cAMP-binding proteins CRP and EPAC, domain
assembly in synaptic proteins, protein-DNA interactions, cytochrome P450
inhibition, and the repurposing of drugs to target the SARS-CoV-2 nsp13
helicase. While crystallography offers high resolution detail of a
molecule and its interactions many structural studies are limited by the
possible: the study of static structures. BioSAXS opens up an avenue to
the study of dynamic and even unstructured molecules of almost any
size, from disaccharides to viral particles. At it’s simplest the
assembly, oligomerization state, or domain organization can be
confirmed, determined, or modeled. At its most complex the distribution
of multiple conformational states may be determined. BioSAXS offers a
tool for the validation of Molecular Dynamics simulations, which in
reciprocity provides molecular models for the analysis of SAXS data.
BioSAXS analysis is a powerful addition to any structural study, be it
crystallography, electron microscopy, or NMR.