Abstract While the structure of proteins can now be predicted from sequence with high certainty, the prediction of protein functional dynamics remains to be achieved. Progress towards this goal will require a much larger experimental database of the relationships among sequence, dynamics, and function than currently available. Dynamic transitions that are key to protein function and turnover remain difficult to access and characterize because they have significantly higher free energy than the folded states of proteins and hence are not populated. To access these higher free energy states, proteins must be perturbed. High temperatures often lead to aggregation, while chemical denaturants, because they interact with the entire protein backbone, tend to smooth protein conformational landscapes. In contrast, high hydrostatic pressure represents a continuous and reversible variable that can perturb protein structure locally around internal cavities, leading to partial structural disruption, populating these higher energy states sufficiently for their characterization.
Roche et al. (Thu,) studied this question.