Folding mechanism of β-helical passenger domains from a bacterial

The mechanism of how the virulence factor are secreted through the outer membrane remains unclear.. Many of these proteins come attached to large β-helical passenger domains, which do not appear to be participating in any of their virulence behavior. Experimental results show that the relative stability at the N- and C-terminus of the passenger domain largely affects the secretion rate of these proteins, suggesting that the folding of the β-helix structure plays a role in efficient secretion. Simulation methods to investigate the folding mechanism and kinetics of the passenger domain. Multidimensional replica-exchange umbrella sampling simulations reveal how cooperative folding beginning at C-terminus enhances the kinetics of folding, while steered molecular dynamics simulations show difference in mechanical responses at the N- and C-terminus. We use Markov state modelling to find intermediate folding states as well as possible misfolded structures, that may act as kinetic traps.