The influence of amino acid protonation states on molecular dynamics simulations of the bacterial porin OmpF.
Several groups, including our own, have found molecular dynamics (MD) calculations to result in the size of the pore of an outer membrane bacterial porin, OmpF, to be reduced relative to its size in the x-ray crystal structure. At the narrowest portion of its pore, loop L3 was found to move toward the opposite face of the pore, resulting in decreasing the cross-section area by a factor of approximately 2. In an earlier work, we computed the protonation states of titratable residues for this system and obtained values different from those that had been used in previous MD simulations. Here, we show that MD simulations carried out with these recently computed protonation states accurately reproduce the cross-sectional area profile of the channel lumen in agreement with the x-ray structure. Our calculations include the investigation of the effect of assigning different protonation states to the one residue, D(127), whose protonation state could not be modeled in our earlier calculation. We found that both assumptions of charge states for D(127) reproduced the lumen size profile of the x-ray structure. We also found that the charged state of D(127) had a higher degree of hydration and it induced greater mobility of polar side chains in its vicinity, indicating that the apparent polarizability of the D(127) microenvironment is a function of the D(127) protonation state.
Varma
Sameer
S
Center for Biophysics and Computational Biology, National Center for Supercomputing Applications, Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Chiu
See-Wing
SW
Jakobsson
Eric
E
D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D009010:Monte Carlo Method; D009154:Mutation; D018272:Porins / Q000737:chemistry*; D011487:Protein Conformation; D011522:Protons; D012984:Software; D012997:Solvents; D055672:Static Electricity; D013696:Temperature; D013997:Time Factors
D000596:Amino Acids; D007477:Ions; D008051:Lipid Bilayers; D008055:Lipids; C109237:OmpF protein; D018272:Porins; D011522:Protons; D012997:Solvents