Conformational analysis of replica exchange MD: Temperature-dependent Markov networks for FF amyloid peptides

Recent molecular modeling methods using Markovian descriptions of conformational states of biomolecular systems have led to powerful analysis frameworks that can accurately describe their complex dynamical behavior. In conjunction with enhanced sampling methods, such as replica exchange molecular dynamics (REMD), these frameworks allow the systematic and accurate extraction of transition probabilities between the corresponding states, in the case of Markov state models, and of statistically-optimized transition rates, in the case of the corresponding coarse master equations. However, applying automatically such methods to large molecular dynamics (MD) simulations, with explicit water molecules, remains limited both by the initial ability to identify good candidates for the underlying Markovian states and by the necessity to do so using good collective variables as reaction coordinates that allow the correct counting of inter-state transitions at various lag times. Here, we show that, in cases when represe...