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Continuum electrostatic analysis of irregular ionization and proton allocation in proteins
Author(s) -
Koumanov Assen,
Rüterjans Heinz,
Karshikoff Andrey
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10034
Subject(s) - protonation , chemistry , deprotonation , tautomer , titration curve , ionization , titration , dipole , molecule , computational chemistry , acid dissociation constant , titratable acid , stereochemistry , ion , organic chemistry , aqueous solution , biochemistry
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 p K 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 T 1 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. Proteins 2002;46:85–96. © 2001 Wiley‐Liss, Inc.