Document Detail

Reproducing basic pKa values for turkey ovomucoid third domain using a polarizable force field.
MedLine Citation:
PMID:  19432439     Owner:  NLM     Status:  MEDLINE    
We have extended our previous studies of calculating acidity constants for the acidic residues found in the turkey ovomucoid third domain protein (OMTKY3) by determining the relative pKa values for the basic residues (Lys13, Arg21, Lys29, Lys34, His52, and Lys55). A polarizable force field (PFF) was employed. The values of the pKa were found by direct comparison of energies of solvated protonated and deprotonated forms of the protein. Poisson-Boltzmann (PBF) and surface generalized Born (SGB) continuum solvation models represent the hydration, and a nonpolarizable fixed-charge OPLS-AA force field was used for comparison. Our results indicate that (i) the pKa values of the basic residues can be found in close agreement with the experimental values when a PFF is used in conjunction with the PBF solvation model, (ii) it is sufficient to take into the account only the residues which are in close proximity (hydrogen bonded) to the residue in question, and (iii) the PBF solvation model is superior to the SGB solvation model for these pKa calculations. The average error with the PBF/PFF model is only 0.7 pH unit, compared with 2.2 and 6.1 units for the PBF/OPLS and SGB/OPLS, respectively. The maximum deviation of the PBF/PFF results from the experimental values is 1.7 pH units compared with 6.0 pH units for the PBF/OPLS. Moreover, the best results were obtained while using an advanced nonpolar energy calculation scheme. The overall conclusion is that this methodology and force field are suitable for the accurate assessment of pKa shifts for both acidic and basic protein residues.
Timothy H Click; George A Kaminski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The journal of physical chemistry. B     Volume:  113     ISSN:  1520-6106     ISO Abbreviation:  J Phys Chem B     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-28     Completed Date:  2009-08-10     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  101157530     Medline TA:  J Phys Chem B     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7844-50     Citation Subset:  IM    
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MeSH Terms
Arginine / chemistry
Histidine / chemistry
Hydrogen-Ion Concentration
Lysine / chemistry
Models, Molecular
Ovomucin / chemistry*
Protein Structure, Tertiary
Grant Support
R01 GM074624/GM/NIGMS NIH HHS; R01 GM074624-01A2/GM/NIGMS NIH HHS; R01 GM074624-02/GM/NIGMS NIH HHS; R01 GM074624-03/GM/NIGMS NIH HHS; R01 GM074624-04/GM/NIGMS NIH HHS; R01GM074624/GM/NIGMS NIH HHS
Reg. No./Substance:
37281-36-0/Ovomucin; 4QD397987E/Histidine; 94ZLA3W45F/Arginine; K3Z4F929H6/Lysine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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