Conformational preferences and p K a value of selenocysteine residue

The conformational preferences of the L ‐selenocysteine (Sec) dipeptides with selenol and selenolate groups (Ac‐Sec‐NHMe and Ac‐Sec − ‐NHMe, respectively) and the apparent (i.e., macroscopic) p K a value of the Sec residue have been studied using the dispersion‐corrected density functionals M06‐2X and B2PLYP‐D with the implicit solvation method in the gas phase and in water. In the gas phase, the backbone‐to‐backbone and/or side chain‐to‐backbone hydrogen bonds are found to contribute in stabilizing the most preferred conformations for the Sec and Sec − residues, as seen for the Cys and Cys − residues. However, the polyproline II‐like conformations prevail over the conformations with the backbone‐to‐backbone hydrogen bonds in water because of the weakened hydrogen bonds by the favorable direct interactions between the backbone CO and HN groups and water molecules. The Sec and Sec − residues are found to adopt more various conformations than the Cys and Cys − residues in water, although the most preferred conformations of the neutral and/or anionic forms of the two residues are similar each other in the gas phase and in water. Using the statistically weighted free energies of the Sec and Sec − dipeptides in the gas phase and their solvation free energies, the p K a value of the Sec residue is estimated to be 5.47 at 25°C, which is in good agreement with the experimental value of 5.43 ± 0.02. It is found that the lower p K a value of the selenol side chain for the Sec residue by ∼3 units than the thiol side chain for the Cys residue is ascribed to the higher gas‐phase acidity of the Sec residue. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 345–353, 2011.