Catch bond-like kinetics of helix cracking: Network analysis by molecular dynamics and Milestoning

Abstract

The first events of unfolding of secondary structure under load are considered with Molecular Dynamics simulations and Milestoning analysis of a long helix (126 amino acids). The Mean First Passage Time is a non-monotonic function of the applied load with a maximum of 3.6 ns at about 20 pN. Network analysis of the reaction space illustrates the opening and closing of an off-pathway trap that slows unfolding at intermediate load levels. It is illustrated that the nature of the reaction networks changes as a function of load, demonstrating that the process is far from one-dimensional.

Markovian and Non-Markovian Modeling of Membrane Dynamics with Milestoning

“…To ensure the significance of this comparison we assess the error bars in the calculations using a statistical model that we developed earlier. 29 In brief, the model is set as follows: A transition matrix element, $K_{\alpha \beta }$, is estimated from an ensemble of trajectories initiated at milestone $\alpha$. Each of the trajectories yields a weight of 0 or 1 for the transition.…”

“…This transition kernel is estimated from molecular dynamics trajectories. We can use a single long trajectory, which is chopped to many small fragments between milestones 29,30 , or many short trajectories 30–33 initiated on one milestone and terminated on another. From the trajectories we can determine instances in which the milestones $\mathrm{normal\Delta }\rho (\mathbf{r})$ and $\mathrm{normal\Delta }\rho \prime (\mathbf{r}\prime )$ are passed in sequence.…”

Extracting the diffusion tensor from molecular dynamics simulation with Milestoning

“…The errors are then propagated to the diffusion and the force. A normal distribution of the errors was assumed in an earlier study 46 which is an approximation to the expression derived here.…”

Perspective: Reaches of chemical physics in biology

“…40 The structural basis of this behavior, referred to as catch bond, is not fully understood. In an interesting paper Kreuzer and Elber 41 show using all atom molecular dynamics simulations that a simple helix exhibits catch bond behavior force at low forces before making a transition to the slip bond behavior. The findings are linked to complex network of connected states in this simple system.…”