It has been a long-standing and intriguing issue to develop robust methods to identify metastable states and interstate transitions from simulations or experimental data to understand the functional conformational changes of proteins. It is usually hard to define the complicated boundaries of the states in the conformational space using most of the existing methods, and they often lead to parameter-sensitive results. Here, we present a new approach, visualized Trajectory Map (vTM), to identify the metastable states and the rare interstate transitions, by considering both the conformational similarity and the temporal successiveness of conformations. The vTM is able to give a nonambiguous description of slow dynamics. The case study of a β-hairpin peptide shows that the vTM can reveal the states and transitions from all-atom MD trajectory data even when a single observable (i.e, one-dimensional reaction coordinate) is used. We also use the vTM to refine the folding/unfolding mechanism of HP35 in explicit water by analyzing a 125 μs all-atom MD trajectory and obtain folding/unfolding rates of about 1/μs, which are in good agreement with the experimental values.

We studied theoretically the translocation dynamics of polymer chain through a nanochannel, taking the position of its leading end in the channel as the reaction coordinate. The free energy profile of the translocation is found linear for homogeneous channels, and the driven force (the spatial derivative of free energy) is found insensitive to the chain length of the polymer, the length of the channel, whereas it decreases monotonically as the radius of the channel increases. Our Letter provides more direct understanding on recent experiments of polymer translocation.Graphical abstractHighlights► We theoretically study polymer translocation through finite-length nanochannels. ► The position of polymer leading end is applied as reaction coordinate. ► The free energy of polymer is a linear function of the reaction coordinate. ► The entropy driven force is insensitive to most of system parameters. ► The theoretical results are helpful in understanding recent experiments.