Trapping Moving Targets with Small Molecules
Gregory M. Lee and
Charles S. Craik*
Structure-based drug design traditionally uses static protein
models as inspirations for focusing on "active" site targets.
Allosteric regulation of biological macromolecules, however,
is affected by both conformational and dynamic properties of
the protein or protein complex and can potentially lead to more
avenues for therapeutic development. We discuss the advantages
of searching for molecules that conformationally trap a macromolecule
in its inactive state. Although multiple methodologies exist
to probe protein dynamics and ligand binding, our current discussion
highlights the use of nuclear magnetic resonance spectroscopy
in the drug discovery and design process.
* To whom correspondence should be addressed. E-mail: craik{at}cgl.ucsf.edu
