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. 2001 Sep;81(3):1632–1642. doi: 10.1016/S0006-3495(01)75817-1

Contribution of translational and rotational motions to molecular association in aqueous solution.

Y B Yu 1, P L Privalov 1, R S Hodges 1
PMCID: PMC1301641  PMID: 11509376

Abstract

Much uncertainty and controversy exist regarding the estimation of the enthalpy, entropy, and free energy of overall translational and rotational motions of solute molecules in aqueous solutions, quantities that are crucial to the understanding of molecular association/recognition processes and structure-based drug design. A critique of the literature on this topic is given that leads to a classification of the various views. The major stumbling block to experimentally determining the translational/rotational enthalpy and entropy is the elimination of vibrational perturbations from the measured effects. A solution to this problem, based on a combination of energy equi-partition and enthalpy-entropy compensation, is proposed and subjected to verification. This method is then applied to analyze experimental data on the dissociation/unfolding of dimeric proteins. For one translational/rotational unit at 1 M standard state in aqueous solution, the results for enthalpy (H degrees (tr)), entropy (S degrees (tr)), and free energy (G degrees (tr)) are H (degrees) (tr) = 4.5 +/- 1.5RT, S (degrees) (tr) = 5 +/- 4R, and G (degrees) (tr) = 0 +/- 5RT. Therefore, the overall translational and rotational motions make negligible contribution to binding affinity (free energy) in aqueous solutions at 1 M standard state.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amzel L. M. Loss of translational entropy in binding, folding, and catalysis. Proteins. 1997 Jun;28(2):144–149. [PubMed] [Google Scholar]
  2. Andrews P. R., Craik D. J., Martin J. L. Functional group contributions to drug-receptor interactions. J Med Chem. 1984 Dec;27(12):1648–1657. doi: 10.1021/jm00378a021. [DOI] [PubMed] [Google Scholar]
  3. Brady G. P., Sharp K. A. Energetics of cyclic dipeptide crystal packing and solvation. Biophys J. 1997 Feb;72(2 Pt 1):913–927. doi: 10.1016/s0006-3495(97)78725-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brady G. P., Sharp K. A. Entropy in protein folding and in protein-protein interactions. Curr Opin Struct Biol. 1997 Apr;7(2):215–221. doi: 10.1016/s0959-440x(97)80028-0. [DOI] [PubMed] [Google Scholar]
  5. Böhm H. J. The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure. J Comput Aided Mol Des. 1994 Jun;8(3):243–256. doi: 10.1007/BF00126743. [DOI] [PubMed] [Google Scholar]
  6. Dunitz J. D. Win some, lose some: enthalpy-entropy compensation in weak intermolecular interactions. Chem Biol. 1995 Nov;2(11):709–712. doi: 10.1016/1074-5521(95)90097-7. [DOI] [PubMed] [Google Scholar]
  7. Erickson H. P. Co-operativity in protein-protein association. The structure and stability of the actin filament. J Mol Biol. 1989 Apr 5;206(3):465–474. doi: 10.1016/0022-2836(89)90494-4. [DOI] [PubMed] [Google Scholar]
  8. Finkelstein A. V., Janin J. The price of lost freedom: entropy of bimolecular complex formation. Protein Eng. 1989 Oct;3(1):1–3. doi: 10.1093/protein/3.1.1. [DOI] [PubMed] [Google Scholar]
  9. Gilson M. K., Given J. A., Bush B. L., McCammon J. A. The statistical-thermodynamic basis for computation of binding affinities: a critical review. Biophys J. 1997 Mar;72(3):1047–1069. doi: 10.1016/S0006-3495(97)78756-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gómez J., Freire E. Thermodynamic mapping of the inhibitor site of the aspartic protease endothiapepsin. J Mol Biol. 1995 Sep 22;252(3):337–350. doi: 10.1006/jmbi.1995.0501. [DOI] [PubMed] [Google Scholar]
  11. Holtzer A. The "cratic correction" and related fallacies. Biopolymers. 1995 Jun;35(6):595–602. doi: 10.1002/bip.360350605. [DOI] [PubMed] [Google Scholar]
  12. Janin J. Elusive affinities. Proteins. 1995 Jan;21(1):30–39. doi: 10.1002/prot.340210105. [DOI] [PubMed] [Google Scholar]
  13. Karplus M., Janin J. Comment on: 'The entropy cost of protein association'. Protein Eng. 1999 Mar;12(3):185–187. doi: 10.1093/protein/12.3.185. [DOI] [PubMed] [Google Scholar]
  14. Liu L., Guo Q. X. Isokinetic relationship, isoequilibrium relationship, and enthalpy-entropy compensation. Chem Rev. 2001 Mar;101(3):673–695. doi: 10.1021/cr990416z. [DOI] [PubMed] [Google Scholar]
  15. Miyamoto S., Kollman P. A. Absolute and relative binding free energy calculations of the interaction of biotin and its analogs with streptavidin using molecular dynamics/free energy perturbation approaches. Proteins. 1993 Jul;16(3):226–245. doi: 10.1002/prot.340160303. [DOI] [PubMed] [Google Scholar]
  16. Murphy K. P., Xie D., Garcia K. C., Amzel L. M., Freire E. Structural energetics of peptide recognition: angiotensin II/antibody binding. Proteins. 1993 Feb;15(2):113–120. doi: 10.1002/prot.340150203. [DOI] [PubMed] [Google Scholar]
  17. Murphy K. P., Xie D., Thompson K. S., Amzel L. M., Freire E. Entropy in biological binding processes: estimation of translational entropy loss. Proteins. 1994 Jan;18(1):63–67. doi: 10.1002/prot.340180108. [DOI] [PubMed] [Google Scholar]
  18. Novotny J., Bruccoleri R. E., Saul F. A. On the attribution of binding energy in antigen-antibody complexes McPC 603, D1.3, and HyHEL-5. Biochemistry. 1989 May 30;28(11):4735–4749. doi: 10.1021/bi00437a034. [DOI] [PubMed] [Google Scholar]
  19. Page M. I., Jencks W. P. Entropic contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1678–1683. doi: 10.1073/pnas.68.8.1678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. STEINBERG I. Z., SCHERAGA H. A. Entropy changes accompanying association reactions of proteins. J Biol Chem. 1963 Jan;238:172–181. [PubMed] [Google Scholar]
  21. Spolar R. S., Record M. T., Jr Coupling of local folding to site-specific binding of proteins to DNA. Science. 1994 Feb 11;263(5148):777–784. doi: 10.1126/science.8303294. [DOI] [PubMed] [Google Scholar]
  22. Tamura A., Privalov P. L. The entropy cost of protein association. J Mol Biol. 1997 Nov 14;273(5):1048–1060. doi: 10.1006/jmbi.1997.1368. [DOI] [PubMed] [Google Scholar]
  23. Tidor B., Karplus M. The contribution of vibrational entropy to molecular association. The dimerization of insulin. J Mol Biol. 1994 May 6;238(3):405–414. doi: 10.1006/jmbi.1994.1300. [DOI] [PubMed] [Google Scholar]
  24. Villa J., Strajbl M., Glennon T. M., Sham Y. Y., Chu Z. T., Warshel A. How important are entropic contributions to enzyme catalysis? Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11899–11904. doi: 10.1073/pnas.97.22.11899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Zhou N. E., Kay C. M., Hodges R. S. Disulfide bond contribution to protein stability: positional effects of substitution in the hydrophobic core of the two-stranded alpha-helical coiled-coil. Biochemistry. 1993 Mar 30;32(12):3178–3187. doi: 10.1021/bi00063a033. [DOI] [PubMed] [Google Scholar]

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