Assessing and Manipulating Protein Folding Dynamics

Abstract

While the folding energy landscape theory provides an overarching framework for understanding how proteins fold, a mechanistic elucidation of the folding mechanism of any specific protein still requires characterization of its conformational dynamics at the molecular level. However, this requirement amounts to a significant challenge to experimentalists as none of the existing techniques is capable of taking conformational snapshots along the folding pathway(s) with the necessary temporal and structural resolutions, let alone to directly and realistically determine the underlying folding free energy surface(s). In this talk, we will discuss several spectroscopic methods that could significantly improve our ability to assess the folding dynamics of specific structural elements in protein folding kinetic studies and, in some cases, to distinguish between different folding pathways. In addition, we will present examples showing how certain details of the folding free energy landscape of interest can be revealed by manipulating the corresponding folding dynamics via structural cross-linking.