%0 Journal Article
%T Unfolding Ubiquitin by force: water mediated H-bond destabilization
%A Germ¨¢n Pab¨®n
%A Mario Amzel
%J Universitas Scientiarum
%D 2012
%I Pontificia Universidad Javeriana
%X Using the ¡°pull and wait¡± (PNW) simulation protocol at 300 K, we studied the unfolding by force of an ubiquitin molecule. PNW was implemented in the CHARMM program using an integration time step of 1 fs and a uniform dielectric constant of 1. The ubiquitin molecule, initially solvated, was put under mechanical stress, exerting forces from different directions. The rupture of five hydrogen bonds between parallel strands ¦Â1 and ¦Â5 takes place during the extension from 13 to 15  , defines a mechanical barrier for unfolding and dominates the point of maximum unfolding force. The simulations described here show that given adequate time, a small applied force can destabilize those five H-bonds relative to the bonds that can be created to water molecules; allowing the formation of stable H-bonds between a single water molecule and the donor and acceptor groups of the interstrand H-bonds. Thus, simulations run with PNW show that the force is not responsible for ¡°ripping apart¡± the backbone H-bonds; it merely destabilizes them making them less stable than the H-bonds they can make with water. Additional simulations show that the force necessary to destabilize the H-bonds and allow them to be replaced by H-bonds to water molecules depends strongly on the pulling direction. By using a simulation protocol that allows equilibration at each extension we have been able to observe the details of the events leading to the unfolding of ubiquitin by mechanical force.
%U http://revistas.javeriana.edu.co/index.php/scientarium/article/view/4024/3104