Thermal Stability and Unfolding Pathways of Hyperthermophilic and Mesophilic Periplasmic binding proteins studied by Molecular Dynamics Simulation

Although several cellular and structural studies have been reported, a description of the thermostability of RBP at the molecular level remains elusive. Focused on the hyperthermophilic Thermoytoga maritima RBP (tmRBP) and mesophilic Escherichia coli homolog (ecRBP), we applied molecular dynamics simulations at four different temperatures (300, 380, 450, and 500 K) to obtain a deeper insight into the structural features responsible for the reduced thermostability of the ecRBP.

The simulations results indicate that there are distinct structural differences in the unfolding pathway between the two homologues and the ecRBP unfolds faster than the hyperthermophilic homologues at certain temperatures in accordance with the lower thermal stability found experimentally. Essential dynamics analysis uncovers that the essential subspaces of ecRBP and tmRBP are non-overlapping and these two proteins show different direction of motion within the simulations trajectories.