proteinrest

Proteinrest is a term proposed to describe the resting or baseline conformational ensemble that a protein occupies in the absence of external triggers such as ligands, post-translational modifications, or mechanical forces. It is used to contrast with activated, ligand-bound, or stimulated states and to emphasize the dynamic nature of proteins as ensembles rather than single static structures. The concept treats proteinrest as a context-dependent collection of low-energy conformations that prevail under defined conditions (temperature, pH, ionic strength) and can shift with changes in the cellular environment.

Characteristics of proteinrest include conformational flexibility, diverse populations, and rapid interconversion among microstates. Measurement relies on an ensemble perspective, typically integrating molecular dynamics simulations with experimental data such as NMR relaxation rates, hydrogen-deuterium exchange, small-angle X-ray scattering, cryo-EM particle ensembles, or FRET efficiency distributions. A central idea is that the resting ensemble provides a baseline from which functional transitions occur and that perturbations can reweight the ensemble without requiring a large unfolding event.

Applications of the concept include informing studies of allosteric mechanisms, understanding misfolding or aggregation risk, and aiding ligand design by seeking compounds that stabilize or modulate the proteinrest ensemble. Critically, proteinrest is not universally standardized and often overlaps with existing concepts such as the native state, apo form, or resting-state conformations used in protein dynamics research. As such, its use emphasizes ensemble interpretation over single-structure descriptions.