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 journalArticle

79 Citations (Scopus)

Abstract

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
Volume106
Issue number13
DOIs
StatePublished - Apr 4 2002
Externally publishedYes

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Ovomucin
lysine
Quantum theory
Boltzmann equation
Lysine
quantum mechanics
proteins
Proteins
predictions
Solvation
Functional groups
solvation
amino acids
Amino acids
fragments
methodology
continuums
deviation
Amino Acids
acids

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

The prediction of protein pKa's using QM/MM : The pKa of lysine 55 in turkey ovomucoid third domain. / Li, Hui; Hains, Alexander W.; Everts, Joshua E.; Robertson, Andrew D.; Jensen, Jan H.

In: Journal of Physical Chemistry B, Vol. 106, No. 13, 04.04.2002, p. 3486-3494.

Research output: Contribution to journalArticle

Li, Hui ; Hains, Alexander W. ; Everts, Joshua E. ; Robertson, Andrew D. ; Jensen, Jan H. / The prediction of protein pKa's using QM/MM : The pKa of lysine 55 in turkey ovomucoid third domain. In: Journal of Physical Chemistry B. 2002 ; Vol. 106, No. 13. pp. 3486-3494.
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