Protein dynamics

protein dynamics describes structural fluctuations and transitions between conformations of a protein. Functional interpretation needs the conformational populations and timescales of these transitions, not merely a list of static structures.

A conformational population is the fraction of otherwise specified molecules occupying a particular conformation. It describes how a conformational ensemble is distributed, rather than a single mean structure. For two equilibrium conformations of the same molecular composition, let $G_A,G_B$ be their effective molar Gibbs free energies at fixed temperature and pressure. Their population ratio isThe effective free energies include each state's internal degeneracy. A higher-free-energy state can remain appreciably populated even though it is not the most common structure.

Populations and exchange rates are different observables. A two-state kinetic model $A\rightleftarrows B$ with rates $k_{AB},k_{BA}$ has equilibrium balance $k_{AB}{p}_A=k_{BA}{p}_B$. Multiplying both rates by ten leaves the populations unchanged but speeds exchange tenfold.

In a primary nuclear magnetic resonance study of cyclophilin A, measurements detected coordinated conformational exchange in the free enzyme and related motions during turnover, illustrating why a static structure is insufficient to describe enzyme dynamics.^[ref] Inferring a catalytic mechanism requires the relevant exchange and reaction rates as well as the conformational populations.

The distribution of molecular conformations and their interconversion in an enzyme under specified chemical conditions. A minor conformational population can be functionally important even when a mean structure changes little.

A model-based measure of the amplitude of internal bond-vector motion inferred from suitable relaxation measurements. It requires assumptions about overall tumbling and timescale separation.