DOI: 10.1073/pnas.0700188104. Accurate, conformation-dependent predictions of solvent effects on protein ionization constants

Accurate, conformation-dependent predictions of solvent effects on protein ionization constants

10.1073/pnas.0700188104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Predicting how aqueous solvent modulates the conformational transitions and influences the pKa values that regulate the biological functions of biomolecules remains an unsolved challenge. To address this problem, we developed FDPB_MF, a rotamer repacking method that exhaustively samples side chain conformational space and rigorously calculates multibody protein–solvent interactions. FDPB_MF predicts the effects on pKa values of various solvent exposures, large ionic strength variations, strong energetic couplings, structural reorganizations and sequence mutations. The method achieves high accuracy, with root mean square deviations within 0.3 pH unit of the experimental values measured for turkey ovomucoid third domain, hen lysozyme, Bacillus circulans xylanase, and human and Escherichia coli thioredoxins. FDPB_MF provides a faithful, quantitative assessment of electrostatic interactions in biological macromolecules.

Bibliography

Barth, P., Alber, T., & Harbury, P. B. (2007). Accurate, conformation-dependent predictions of solvent effects on protein ionization constants. Proceedings of the National Academy of Sciences, 104(12), 4898â4903.

Authors 3

P. Barth (first)
T. Alber (additional)
P. B. Harbury (additional)

References 38 Referenced 43

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Dates

Type	When
Created	18 years, 5 months ago (March 14, 2007, 8:40 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 3:33 p.m.)
Indexed	1 month, 1 week ago (July 11, 2025, 6:40 a.m.)
Issued	18 years, 5 months ago (March 20, 2007)
Published	18 years, 5 months ago (March 20, 2007)
Published Online	18 years, 5 months ago (March 20, 2007)
Published Print	18 years, 5 months ago (March 20, 2007)

Funders 0

None

BibTeX

@article{Barth_2007, title={Accurate, conformation-dependent predictions of solvent effects on protein ionization constants}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0700188104}, DOI={10.1073/pnas.0700188104}, number={12}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Barth, P. and Alber, T. and Harbury, P. B.}, year={2007}, month=mar, pages={4898–4903} }

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