TY - JOUR
T1 - The influence of amino acid protonation states on molecular dynamics simulations of the bacterial porin OmpF
AU - Varma, Sameer
AU - Chiu, See Wing
AU - Jakobsson, Eric
N1 - Funding Information:
This work was supported by National Institutes of Health grant R01GM054651-08 and by the U.S. Dept. of Energy’s Genomics: GTL program ( www.doegenomestolife.org ) under project “Carbon Sequestration in Synechococcus Sp .: from Molecular Machines to Hierarchical Modeling” ( www.genomes-to-life.org ).
PY - 2006/1
Y1 - 2006/1
N2 - 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 ∼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, D127, whose protonation state could not be modeled in our earlier calculation. We found that both assumptions of charge states for D127 reproduced the lumen size profile of the x-ray structure. We also found that the charged state of D127 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 D127 microenvironment is a function of the D127 protonation state.
AB - 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 ∼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, D127, whose protonation state could not be modeled in our earlier calculation. We found that both assumptions of charge states for D127 reproduced the lumen size profile of the x-ray structure. We also found that the charged state of D127 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 D127 microenvironment is a function of the D127 protonation state.
UR - http://www.scopus.com/inward/record.url?scp=33646134384&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646134384&partnerID=8YFLogxK
U2 - 10.1529/biophysj.105.059329
DO - 10.1529/biophysj.105.059329
M3 - Article
C2 - 16183883
AN - SCOPUS:33646134384
VL - 90
SP - 112
EP - 123
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 1
ER -