Using dynamic force spectroscopy, protein engineering, structural studies and molecular dynamics simulations to investigate the effect of force on a protein unfolding landscape.

摘要

The protein folding problem is usually expressed in terms of asking how proteins fold from a linear unfolded amino acid chain to a specific three-dimensional shape, in short (ms-s) timescales.As a rule, folding of evolved sequences is highly cooperative, avoiding kinetic traps or alternatively folded structures, and the pathway of folding is robust to changes in conditions and to mutation.We describe proteins as folding on energy landscapes, which have been investigated for a number of proteins by combining experiment and theory.It is a paradigm of these studies that the folding and unfolding processes are the direct reverse of each other. Many proteins experience force in vivo.To maintain their structure they have to remain folded under physiological forces.These mechanically active proteins have an evolved energy landscape that gives them mechanical strength.This is achieved by maintaining a high energy barrier to unfolding when directional force is applied.By investigating the unfolding of a single protein in detail, both in the presence and the absence of force, it is possible to investigate how force alters the protein unfolding landscape.