How do the protonation states of E296 and D312 in OmpF and D299 and D315 in homologous OmpC affect protein structure and dynamics? Simulation studies

• Different protonation states of E296(D299) and D312(315) in OmpF and OmpC promote the large-­scale deviation in protein structure and dynamics.
• Either E296(D299) or D312(315) should be charged to preserve L3 motion.
• OmpC is more resistant to different protonation states of E296(D299) and D312(315) than OmpF.
• The tip of L3 controls pore cavity in bothporins.

In this study, the structural and dynamic properties of two major porins (OmpF and OmpC) in Escherichia coli are investigated using molecular dynamics (MD) simulations. Both porins have the extracellular loop L3 folded halfway through the pore to form a constriction area. The solute influx and efflux are controlled by the L3 movement. E296 and D312 in OmpF and homologous D299 and D315 in OmpC located on the barrel wall are found to play a key role in L3 gating activity. All possible charged states of both E296(D299) and D312(315) are applied in this study to observe changes in overall structure and especially L3 movement. The results show that different protonation states of both residues cause the large-scale deviations in structure and pore cavity especially in OmpF. Fully charged E296(D299) and D312(315) increase the protein flexibility significantly. Deprotonating at least one of E296(D299) and D312(315) helps to fasten L3 to the barrel wall and maintain pore size. Lacking of interactions with D312(315) can lead to the pore closure in OmpF. Comparing with OmpC, not only is OmpF less stable, but it is also more sensitive to the charge states of both E296(D299) and D312(315).

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