Biophys J, February 2000, p. 584-589, Vol. 78, No. 2

Mechanical Unfolding of a -Hairpin Using Molecular Dynamics

Zev Bryant,^* Vijay S. Pande, and Daniel S. Rokhsar

Departments of  ^*Molecular and Cell Biology and  Physics, University of California at Berkeley, Berkeley, California 94720-7300 and  Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

Single-molecule mechanical unfolding experiments have the potential to provide insights into the details of protein folding pathways. To investigate the relationship between force-extension unfolding curves and microscopic events, we performed molecular dynamics simulations of the mechanical unfolding of the C-terminal hairpin of protein G. We have studied the dependence of the unfolding pathway on pulling speed, cantilever stiffness, and attachment points. Under conditions that generate low forces, the unfolding trajectory mimics the untethered, thermally accessible pathway previously proposed based on high-temperature studies. In this stepwise pathway, complete breakdown of backbone hydrogen bonds precedes dissociation of the hydrophobic cluster. Under more extreme conditions, the cluster and hydrogen bonds break simultaneously. Transitions between folding intermediates can be identified in our simulations as features of the calculated force-extension curves.

Biophys J, February 2000, p. 584-589, Vol. 78, No. 2
© 2000 by the Biophysical Society   0006-3495/00/02/584/06  $2.00

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