Murray State University
Hydrogen Bonding is the Prime Determinant of Carboxyl pKa Values at N-termini of Alpha-Helices
Institution
Murray State University
Faculty Advisor/ Mentor
Pablo Molina
Abstract
Experimentally determined mean pKa values of carboxyl residues located at N-termini of alpha-helices are lower than their overall mean values. Here, we perform three types of analyses to account for this phenomenon. We estimate the magnitude of the helix macrodipole to determine its potential role in lowering carboxyl pKa values at N-termini. No correlation between the magnitude of the macro-dipole and the pKa values is observed. Using the pKa program propKa we compare the molecular surroundings of 18 N-termini carboxyl residues versus 233 protein carboxyl groups from a previously studied database. While pKa lowering interactions at N-termini are similar in nature to those encountered in other protein regions, pKa lowering backbone and sidechain hydrogen bonds appear in greater number at N-termini For both Asp and Glu, there are about 0.5 more hydrogen bonds per residue at N-termini than in other protein regions which can be used to explain their lower than average pKa values. Using a QM-based pKa prediction model, we investigate the chemical environment of the two lowest Asp and the two lowest Glu pKa values at N-termini so as to quantify the effect of various pKa determinants. We show that local interactions suffice to account for the acidity of carboxyl residues at N-termini. The effect of the helix dipole on carboxyl pKa values, if any, is marginal. Backbone amide hydrogen bonds constitute the single biggest contributor to the lowest carboxyl pKa values at N-termini. Their estimated pKa lowering effects range from about 1.0 to 1.9 pKa units.
Hydrogen Bonding is the Prime Determinant of Carboxyl pKa Values at N-termini of Alpha-Helices
Experimentally determined mean pKa values of carboxyl residues located at N-termini of alpha-helices are lower than their overall mean values. Here, we perform three types of analyses to account for this phenomenon. We estimate the magnitude of the helix macrodipole to determine its potential role in lowering carboxyl pKa values at N-termini. No correlation between the magnitude of the macro-dipole and the pKa values is observed. Using the pKa program propKa we compare the molecular surroundings of 18 N-termini carboxyl residues versus 233 protein carboxyl groups from a previously studied database. While pKa lowering interactions at N-termini are similar in nature to those encountered in other protein regions, pKa lowering backbone and sidechain hydrogen bonds appear in greater number at N-termini For both Asp and Glu, there are about 0.5 more hydrogen bonds per residue at N-termini than in other protein regions which can be used to explain their lower than average pKa values. Using a QM-based pKa prediction model, we investigate the chemical environment of the two lowest Asp and the two lowest Glu pKa values at N-termini so as to quantify the effect of various pKa determinants. We show that local interactions suffice to account for the acidity of carboxyl residues at N-termini. The effect of the helix dipole on carboxyl pKa values, if any, is marginal. Backbone amide hydrogen bonds constitute the single biggest contributor to the lowest carboxyl pKa values at N-termini. Their estimated pKa lowering effects range from about 1.0 to 1.9 pKa units.