The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized.
The historical record is explored from both biochemical and theoretical perspectives …

▪ Abstract Molecular motions are widely regarded as contributing factors in many aspects of
protein function. The enzyme dihydrofolate reductase (DHFR), and particularly that from …

We used nuclear magnetic resonance relaxation dispersion to characterize higher energy
conformational substates of Escherichia coli dihydrofolate reductase. Each intermediate in …

The mechanism of ligand binding coupled to conformational changes in macromolecules
has recently attracted considerable interest. The 2 limiting cases are the “induced fit” …

Conformational dynamics play a key role in enzyme catalysis. Although protein motions
have clear implications for ligand flux, a role for dynamics in the chemical step of enzyme …

We describe a new dynamic kinetic simulation program that allows multiple data sets to be fit
simultaneously to a single model based on numerical integration of the rate equations …

The reaction catalyzed by Escherichia coli dihydrofolate reductase (ecDHFR) cycles through
five detectable kinetic intermediates: holoenzyme, Michaelis complex, ternary product …

Numerous clinical trials using folic acid for prevention of cardiovascular disease, stroke,
cognitive decline, and neural tube defects have been completed or are underway. Yet, all …

Recent work indicates a general architecture for proteins in which sparse networks of
physically contiguous and coevolving amino acids underlie basic aspects of structure and …

Molecular dynamics are essential for protein function. In some cases these dynamics involve
the interconversion between ground state, highly populated conformers and less populated …