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

TL;DR

This paper develops a geometric model of protein folding energy landscapes during synthesis on the ribosome, integrating cotranslational folding into energy landscape theory using differential geometry.

Contribution

It introduces a nested energy landscape framework for cotranslational folding, extending traditional energy landscape theory with a geometric approach.

Findings

Defines a natural nested energy landscape for cotranslational folding

Uses differential geometry to analyze folding on the ribosome

Derives conditions for effective cotranslational folding

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.