Domain topology, stability, and translation speed determine mechanical force generation on the ribosome

Significance Mechanochemistry, the influence of molecular-scale mechanical forces on chemical processes, can occur on actively translating ribosomes through the force-generating actions of motor proteins and the cotranslational folding of domains. Such forces are transmitted to the ribosome’s catalytic core and alter rates of protein synthesis, representing a form of mechanical allosteric communication. These changes in translation–elongation kinetics are biologically important because they can influence protein structure, function, and localization within a cell. Many fundamental questions are unresolved concerning the properties of protein domains that determine mechanical force generation; the effect of translation speed on this force; and exactly how, at the molecular level, force is generated. In this study we answer these questions using molecular simulations and statistical mechanical modeling.