Highlights•Protein motions are critical for allostery.•Often optimal allosteric pathways exhibit
synchronous motions.•Conservative mutations can dramatically disrupt motions and …

Allostery is a ubiquitous biological mechanism in which a distant binding site is coupled to
and drastically alters the function of a catalytic site in a protein. Allostery provides a high …

Determining the principal energy-transfer pathways responsible for allosteric communication
in biomolecules remains challenging, partially due to the intrinsic complexity of the systems …

Deciphering the molecular mechanisms of enzymatic allosteric regulation requires the
structural characterization of functional states and also their time evolution toward the …

ATP-competitive inhibitors are currently the largest class of clinically approved drugs for
protein kinases. By targeting the ATP-binding pocket, these compounds block the catalytic …

Allosteric drugs have the potential to revolutionize biomedicine due to their enhanced
selectivity and protection against overdosage. However, we need to better understand …

The phenomenon of chemical or conformational exchange in NMR spectroscopy has
enabled detailed characterization of time-dependent aspects of biomolecular function …

A fundamental question in protein science is where allosteric hotspots–residues critical for
allosteric signaling–are located, and what properties differentiate them. We carried out deep …

Imidazole glycerol phosphate synthase (HisFH) is a heterodimeric bienzyme complex
operating at a central branch point of metabolism. HisFH is responsible for the HisH …

Allosteric regulation plays a central role in orchestrating diverse cellular processes. A
prerequisite for allostery is a flexible biomolecule within which two distal sites can …