biostudies-literatureZimmer MHNational Institutes of HealthNIGMS NIH HHS2425-2435https://www.ebi.ac.uk/biostudies/studies/S-EPMC8390854biostudies-literatureUnknown120(12)Force-sensitive arrest peptides regulate protein biosynthesis by stalling the ribosome as they are translated. Synthesis can be resumed when the nascent arrest peptide experiences a pulling force of sufficient magnitude to break the stall. Efficient stalling is dependent on the specific identity of a large number of amino acids, including amino acids that are tens of angstroms away from the peptidyl transferase center (PTC). The mechanism of force-induced restart and the role of these essential amino acids far from the PTC is currently unknown. We use hundreds of independent molecular dynamics trajectories spanning over 120 μs in combination with kinetic analysis to characterize multiple barriers along the force-induced restart pathway for the arrest peptide SecM. We find that the essentiaBiophysical journalForce transduction creates long-ranged coupling in ribosomes stalled by arrest peptides.PMC8390854R01 GM116961R01 GM125063Miller TFZimmer MHNiesen MJMfalseForce transduction creates long-ranged coupling in ribosomes stalled by arrest peptides.Force-sensitive arrest peptides regulate protein biosynthesis by stalling the ribosome as they are translated. Synthesis can be resumed when the nascent arrest peptide experiences a pulling force of sufficient magnitude to break the stall. Efficient stalling is dependent on the specific identity of a large number of amino acids, including amino acids that are tens of angstroms away from the peptidyl transferase center (PTC). The mechanism of force-induced restart and the role of these essential amino acids far from the PTC is currently unknown. We use hundreds of independent molecular dynamics trajectories spanning over 120 μs in combination with kinetic analysis to characterize multiple barriers along the force-induced restart pathway for the arrest peptide SecM. We find that the essentia2021-01-01T00:00:00Z2021 Jun2026-04-08T08:43:59.875Z2025-04-04T22:15:20.985ZS-EPMC83908543393244010.1016/j.bpj.2021.03.041