Generalized Markov State Modeling Method for Nonequilibrium Biomolecular Dynamics: Exemplified on Amyloid β Conformational Dynamics Driven by an Oscillating Electric Field

• DOI: 10.1021/acs.jctc.8b00079
• Publication Date: 2018-05-29T20:54:56Z
• Authors: Bernhard Reuter; Marcus Weber; Konstantin Fackeldey; Susanna Röblitz; Martin E. Garcia
• Keywords: 0301 basic medicine; Kinetics; 03 medical and health sciences; Amyloid beta-Peptides; Electricity; Cluster Analysis; Molecular Dynamics Simulation; Algorithms; Markov Chains; Peptide Fragments

Markov state models (MSMs) have received an unabated increase in popularity in recent years, as they are very well suited for the identification and analysis of metastable states and related kinetics. However, the state-of-the-art Markov state modeling methods and tools enforce the fulfillment of a detailed balance condition, restricting their applicability to equilibrium MSMs. To date, they are unsuitable to deal with general dominant data structures including cyclic processes, which are essentially associated with nonequilibrium systems. To overcome this limitation, we developed a generalization of the common robust Perron Cluster Cluster Analysis (PCCA+) method, termed generalized PCCA (G-PCCA). This method handles equilibrium and nonequilibrium simulation data, utilizing Schur vectors instead of eigenvectors. G-PCCA is not limited to the detection of metastable states but enables the identification of dominant structures in a general sense, unraveling cyclic processes. This is exemplified by application of G-PCCA on nonequilibrium molecular dynamics data of the Amyloid β (1-40) peptide, periodically driven by an oscillating electric field.