Observing the base-by-base search for native structure along transition paths during the folding of single nucleic acid hairpins.

ABSTRACT: Biomolecular folding involves searching among myriad possibilities for the native conformation, but the elementary steps expected from theory for this search have never been detected directly. We probed the dynamics of folding at high resolution using optical tweezers, measuring individual trajectories as nucleic acid hairpins passed through the high-energy transition states that dominate kinetics and define folding mechanisms. We observed brief but ubiquitous pauses in the transition states, with a dwell time distribution that matched microscopic theories of folding quantitatively. The sequence dependence suggested that pauses were dominated by microbarriers from nonnative conformations during the search by each nucleotide residue for the native base-pairing conformation. Furthermore, the

SUBMITTER: Hoffer NQ 

PROVIDER: S-EPMC8670488 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature