Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1998 Jan;7(1):206–210. doi: 10.1002/pro.5560070122

Computation of electrostatic complements to proteins: a case of charge stabilized binding.

L T Chong 1, S E Dempster 1, Z S Hendsch 1, L P Lee 1, B Tidor 1
PMCID: PMC2143805  PMID: 9514276

Abstract

Recent evidence suggests that the net effect of electrostatics is generally to destabilize protein binding due to large desolvation penalties. A novel method for computing ligand-charge distributions that optimize the tradeoff between ligand desolvation penalty and favorable interactions with a binding site has been applied to a model for barnase. The result is a ligand-charge distribution with a favorable electrostatic contribution to binding due, in part, to ligand point charges whose direct interaction with the binding site is unfavorable, but which make strong intra-molecular interactions that are uncloaked on binding and thus act to lessen the ligand desolvation penalty.

Full Text

The Full Text of this article is available as a PDF (5.5 MB).

Selected References

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

  1. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  2. Brünger A. T., Karplus M. Polar hydrogen positions in proteins: empirical energy placement and neutron diffraction comparison. Proteins. 1988;4(2):148–156. doi: 10.1002/prot.340040208. [DOI] [PubMed] [Google Scholar]
  3. Buckle A. M., Schreiber G., Fersht A. R. Protein-protein recognition: crystal structural analysis of a barnase-barstar complex at 2.0-A resolution. Biochemistry. 1994 Aug 2;33(30):8878–8889. doi: 10.1021/bi00196a004. [DOI] [PubMed] [Google Scholar]
  4. Gilson M. K., Honig B. Calculation of the total electrostatic energy of a macromolecular system: solvation energies, binding energies, and conformational analysis. Proteins. 1988;4(1):7–18. doi: 10.1002/prot.340040104. [DOI] [PubMed] [Google Scholar]
  5. Hendsch Z. S., Tidor B. Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci. 1994 Feb;3(2):211–226. doi: 10.1002/pro.5560030206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lounnas V., Wade R. C. Exceptionally stable salt bridges in cytochrome P450cam have functional roles. Biochemistry. 1997 May 6;36(18):5402–5417. doi: 10.1021/bi9622940. [DOI] [PubMed] [Google Scholar]
  7. Misra V. K., Sharp K. A., Friedman R. A., Honig B. Salt effects on ligand-DNA binding. Minor groove binding antibiotics. J Mol Biol. 1994 Apr 29;238(2):245–263. doi: 10.1006/jmbi.1994.1285. [DOI] [PubMed] [Google Scholar]
  8. Novotny J., Bruccoleri R. E., Davis M., Sharp K. A. Empirical free energy calculations: a blind test and further improvements to the method. J Mol Biol. 1997 May 2;268(2):401–411. doi: 10.1006/jmbi.1997.0961. [DOI] [PubMed] [Google Scholar]
  9. Novotny J., Sharp K. Electrostatic fields in antibodies and antibody/antigen complexes. Prog Biophys Mol Biol. 1992;58(3):203–224. doi: 10.1016/0079-6107(92)90006-r. [DOI] [PubMed] [Google Scholar]
  10. Sharp K. A. Electrostatic interactions in hirudin-thrombin binding. Biophys Chem. 1996 Aug 30;61(1):37–49. doi: 10.1016/0301-4622(96)00021-x. [DOI] [PubMed] [Google Scholar]
  11. Sharp K. A., Honig B. Electrostatic interactions in macromolecules: theory and applications. Annu Rev Biophys Biophys Chem. 1990;19:301–332. doi: 10.1146/annurev.bb.19.060190.001505. [DOI] [PubMed] [Google Scholar]
  12. Waldburger C. D., Schildbach J. F., Sauer R. T. Are buried salt bridges important for protein stability and conformational specificity? Nat Struct Biol. 1995 Feb;2(2):122–128. doi: 10.1038/nsb0295-122. [DOI] [PubMed] [Google Scholar]
  13. Wang L., O'Connell T., Tropsha A., Hermans J. Energetic decomposition of the alpha-helix-coil equilibrium of a dynamic model system. Biopolymers. 1996 Oct;39(4):479–489. doi: 10.1002/(sici)1097-0282(199610)39:4<479::aid-bip1>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  14. Wimley W. C., Gawrisch K., Creamer T. P., White S. H. Direct measurement of salt-bridge solvation energies using a peptide model system: implications for protein stability. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2985–2990. doi: 10.1073/pnas.93.7.2985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Xu D., Lin S. L., Nussinov R. Protein binding versus protein folding: the role of hydrophilic bridges in protein associations. J Mol Biol. 1997 Jan 10;265(1):68–84. doi: 10.1006/jmbi.1996.0712. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES