Accounting for the kinetics in order parameter analysis: Lessons from theoretical models and a disordered peptide

Molecular simulations as well as single molecule experiments have been widely analyzed in terms of order parameters, the latter representing candidate probes for the relevant degrees of freedom. Notwithstanding this approach is very intuitive, mounting evidence showed that such descriptions are inaccurate, leading to ambiguous definitions of states and wrong kinetics. To overcome these limitations a framework making use of order parameter fluctuations in conjunction with complex network analysis is investigated. Derived from recent advances in the analysis of single molecule time traces, this approach takes into account the fluctuations around each time point to distinguish between states that have similar values of the order parameter but different dynamics. Snapshots with similar fluctuations are used as nodes of a transition network, the clusterization of which into states provides accurate Markov-state-models of the system under study. Application of the methodology to theoretical models with a noisy order parameter as well as the dynamics of a disordered peptide illustrates the possibility to build accurate descriptions of molecular processes on the sole basis of order parameter time series without using any supplementary information. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4764868]