Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin

¹ Institute of Physics, Polish Academy of Sciences
² Institute of Physics, Academia Sinica, Taiwan

^* To whom correspondence should be addressed. E-mail: masli{at}ifpan.edu.pl.

Submitted on April 26, 2006
Revised on June 10, 2006
Accepted on 22 September 2006

	Abstract

The refolding from stretched initial conformations of ubiquitin (PDB ID: 1ubq) under the quenched force is studied using the C-Go model and the Langevin dynamics. It is shown that the refolding decouples the collapse and folding kinetics. The force quench refolding times scale as f ~ exp(f_qx_f/k_BT), where f_q is the quench force and x_f 0.96 nm is the location of the average transition state along the reaction coordinate given by the end-to-end distance. This value is close to x_f 0.8 nm obtained from the force-clamp experiments [J. M. Fernandez and H. Li, Science 303, 1674-1678 (2004)]. The mechanical and thermal unfolding pathways are studied and compared with the experimental and all-atom simulation results in detail. The sequencing of thermal unfolding was found to be markedly different from the mechanical one. It is found that fixing the N-terminus of ubiquitin changes its mechanical unfolding pathways much more drastically compared to the case when the C-end is anchored. We obtained the distance between the native state and the transition state x_uf 0.24 nm which is in reasonable agreement with the experimental data.

Key Words: Go model, Langevin dynamics, free energy landscape, protein refolding, unfolding pathway