Geometry of the Energy Landscape for a Protein Folding on the Ribosome

Abstract: Energy landscape theory describes how a full-length protein can attain its native fold by sampling only a tiny fraction of all possible structures. Although protein folding is now understood to be concomitant with synthesis on the ribosome, there have been few attempts to modify energy landscape theory by accounting for cotranslational folding. Here we provide a model for cotranslational folding that leads to a natural definition of a nested energy landscape. By applying concepts drawn from submanifold differential geometry, the physics of protein folding on the ribosome can be explored in a quantitative manner and conditions on the nested energy landscapes for a good cotranslational folder are derived.