Does Arginine remain protonated in the lipid membrane? Insights from microscopic pKa calculations
Jejoong Yoo 1 and Qiang Cui 2*
1 Univ. of Wisconsin-Madison
2 University of Wisconsin, Madison
* To whom correspondence should be addressed. E-mail: cui{at}chem.wisc.edu.
Submitted on September 27, 2007
Revised on November 28, 2007
Accepted on 17 December 2007
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Abstract |
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Free energy perturbation calculations are carried out to estimate the effective pKa of an Arginine (Arg) sidechain as a function of its location in the Dipalmitoylphosphatidylcholine (DPPC) bilayer. Similar to previous all-atom simulations of the voltage sensor domain of a potassium channel in the membrane with charged Arg residues, the membrane and water structures are observed to deform to stabilize the charge of the Arg analogue. As a result, the computed pKa is above 7 throughout the membrane although the value is very close to 7 near the center of the bilayer. With additional stabilizations from negatively charged amino acids or lipid molecules, it is reasonable to expect that Arg in membrane proteins (once in the membrane) can adopt the protonated state despite the low dielectric nature of the bulk lipid membrane.
Key Words:
<it>pK<inf>a</inf></it>, free energy perturbation, membrane deformation
