title: Direct sampling of multiple single-molecular rupture dominant pathways involving a multistep transition.
abstract: We report a novel single-molecular rupture mechanism revealed by direct sampling of the dominant pathway using a self-optimized path sampling method. Multiple dominant pathways involving multistep transitions are identified. The rupture may take place via a direct unfolding from the native state to the unfolding state, or through a two-step pathway bypassing a distinct intermediate metastable state (IMS). This scenario facilitates us to propose a three-state kinetic model, which can produce a nonlinear dependence of the rupture time on pulling forces similar to the ones reported in the literature. In particular, molecule conformations in the IMS maintain an elongation of the tail at one terminal, by which external pulling will enhance the relative stability of IMS. Consequently, even though the overall transition rate of the multistep pathway is relatively small, the molecule still has to be ruptured via the multistep pathway rather than the direct pathway. Thus, our work demonstrates an IMS trapping effect induced rupture mechanism involving an abnormal switching from a fast dominant pathway to a slow one.
authors.affiliation: Department of Chemical Physics & Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China. hzhlj@ustc.edu.cn.
authors.forename: Huijun
authors.initials: H
authors.lastname: Jiang
authors.forename: Huai
authors.initials: H
authors.lastname: Ding
authors.forename: Zhonghuai
authors.initials: Z
authors.lastname: Hou
mesh_terms: D001696:Biomechanical Phenomena; D007700:Kinetics; D055595:Mechanical Phenomena; D008958:Models, Molecular; D008968:Molecular Conformation; D017711:Nonlinear Dynamics; D011487:Protein Conformation; D058767:Protein Unfolding