Most proteins fold during biosynthesis on the ribosome, and co-translational folding energetics, pathways and outcomes of many proteins have been found to differ considerably from those in refolding studies. The origin of this folding modulation by the ribosome has remained unknown. Here we have determined atomistic structures of the unfolded state of a model protein on and off the ribosome, which reveal that the ribosome structurally expands the unfolded nascent chain and increases its solvation, resulting in its entropic destabilization relative to the peptide chain in isolation.
View Article and Find Full Text PDFCryogenic electron microscopy (cryo-EM) has emerged as a powerful method for the determination of structures of complex biological molecules. The accurate characterisation of the dynamics of such systems, however, remains a challenge. To address this problem, we introduce cryoENsemble, a method that applies Bayesian reweighting to conformational ensembles derived from molecular dynamics simulations to improve their agreement with cryo-EM data, thus enabling the extraction of dynamics information.
View Article and Find Full Text PDFObjective: Research involving working populations can pose unique ethical and risk evaluation challenges. The purpose of this benchmarking project was to assess how federal agencies and academic institutions approach the interpretation and application of key risk evaluation concepts in research involving workers in their places of employment.
Methods: Key informant interviews were conducted to ascertain current practices related to assessing soundness of research design, determining risk reasonableness and research relatedness of risks, and evaluating the risk of noninvasive clinical tests in occupational settings.
Phys Rev Lett
February 2024
Background: Despite some emerging lessons learned from the COVID-19 pandemic, evidence suggests the world remains largely underprepared for-and vulnerable to-similar threats in the future.
Methods: In 2022, researchers at the US National Institute for Occupational Safety and Health (NIOSH) led a team of volunteers to explore how future disruptions, such as pandemics, might impact work and the practice of occupational safety and health (OSH). This qualitative inquiry was framed as a strategic foresight project and included a series of activities designed to help better understand, prepare for, and influence the future.