The prediction of protein pKa's using QM/MM: The pKa of lysine 55 in turkey ovomucoid third domain

Hui Li, Alexander W. Hains, Joshua E. Everts, Andrew D. Robertson, Jan H. Jensen

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


A computational methodology for pKa predictions of small molecules based on an ab initio quantum mechanics (QM) description of the acid and a linearized Poisson-Boltzmann equation (LPBE) description of bulk solvation using the polarized continuum method is presented. This QM/LPBE method is capable of reproducing the pKa's of several functional groups found in amino acid residues with a root-mean-square deviation from experiment of 0.6 pH units. The practical applicability of the QM/LPBE method is extended to proteins by using a QM description of the ionizable residue and an effective fragment potential (MM) description of the rest of the protein. This QM/MM/LPBE method is used to predict a pKa of the Lys55 residue in turkey ovomucoid third domain of 11.0, which is in good agreement with the experimental value of 11.1.

Original languageEnglish (US)
Pages (from-to)3486-3494
Number of pages9
JournalJournal of Physical Chemistry B
Issue number13
StatePublished - Apr 4 2002
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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