This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.105.059329v1 90/1/112    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varma, S. Articles by Jakobsson, E. Search for Related Content PubMed PubMed Citation Articles by Varma, S. Articles by Jakobsson, E.

The Influence of Amino Acid Protonation States on Molecular Dynamics Simulations of the Bacterial Porin OmpF

Sameer Varma ^*  , See-Wing Chiu   and Eric Jakobsson ^*    ¶

^* Center for Biophysics and Computational Biology, National Center for Supercomputing Applications, Department of Biochemistry, Department of Molecular and Integrative Physiology, and ^¶ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801

Correspondence: Address reprint requests to Eric Jakobsson, Tel.: 217-244-2896; Fax: 217-244-2909; E-mail: jake{at}ncsa.uiuc.edu.

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.

This article has been cited by other articles:

				A. Siroy, C. Mailaender, D. Harder, S. Koerber, F. Wolschendorf, O. Danilchanka, Y. Wang, C. Heinz, and M. Niederweis Rv1698 of Mycobacterium tuberculosis Represents a New Class of Channel-forming Outer Membrane Proteins J. Biol. Chem., June 27, 2008; 283(26): 17827 - 17837. [Abstract] [Full Text] [PDF]

				R. J. Mashl and E. Jakobsson End-Point Targeted Molecular Dynamics: Large-Scale Conformational Changes in Potassium Channels Biophys. J., June 1, 2008; 94(11): 4307 - 4319. [Abstract] [Full Text] [PDF]

				A. C. V. Johansson and E. Lindahl Amino-Acid Solvation Structure in Transmembrane Helices from Molecular Dynamics Simulations Biophys. J., December 15, 2006; 91(12): 4450 - 4463. [Abstract] [Full Text] [PDF]