title: Continuum electrostatic analysis of irregular ionization and proton allocation in proteins.
abstract: Irregular (nonsigmoidal) ionization behavior of titratable groups in proteins is analyzed theoretically, using a computational algorithm designed to count explicitly for tautomers of titratable groups and different locations of polar hydrogens. On the basis of calculations for different model systems (acid-acid, base-base, acid-base pairs, and cluster of three strongly interacting groups), it is demonstrated that the pK values, extracted from nonsigmoidal titration curves by fitting to a sum of Henderson-Hasselbalch equations, do not describe the ionization equilibrium correctly. The conditions for observation of irregular titration curves are derived analytically for the case of arbitrary couple of interacting ionizable groups. A possible relation between irregularly shaped titration curves and tautomerization is also illustrated. The protonation-deprotonation equilibrium of Asp76 in ribonuclease T1 is shown to be coupled to dipole reorientation of a water molecule bound at the protein-solvent interface. This finding provides a new interpretation of the experimentally observed chemical shift of this residue.
authors.affiliation: Karolinska Institutet, Department of Biosciences, Huddinge, Sweden.
authors.forename: Assen
authors.initials: A
authors.lastname: Koumanov
authors.forename: Heinz
authors.initials: H
authors.lastname: Rüterjans
authors.forename: Andrey
authors.initials: A
authors.lastname: Karshikoff
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D006860:Hydrogen Bonding; D007477:Ions; D008958:Models, Molecular; D011487:Protein Conformation; D011522:Protons; D006163:Ribonuclease T1 / Q000737:chemistry; D055672:Static Electricity; D017186:Titrimetry
chemical_list: D000596:Amino Acids; D007477:Ions; D011522:Protons; D001224:Aspartic Acid; D006163:Ribonuclease T1