Skip to main content
SpringerLink
Log in

Modeling protonation equilibria in biomolecules

  • Chapter
Computer Simulation of Biomolecular Systems

Part of the book series: Computer Simulations of Biomolecular Systems ((CSBS,volume 3))

Abstract

pH is one of the fundamental physiological variables. In fact, serious illness is usually associated with deviations of blood pH only a few tenths from the normal value, 7.4. It is very unlikely that the effects of abnormal pH result from the destructive chemical action of protons or hydroxide; if this were the case, a blood pH of 6.8, say, would not be dangerous. It is more likely that the sensitivity of organisms to pH results chiefly from the influence of pH upon the stability and reactivity of the many biomolecules that possess acidic and basic chemical groups. If this is correct, then the ill effects of abnormal pH values should become substantial for pH changes that correspond to free energy changes equal to the thermal energy, ~ RT. Given that ΔΔG = ωpH(RT/loge) = ΔpH(RT/0.43) [1], the critical pH change should be about 0.4. In fact, this defines quite well the range of blood pH values that are tolerable to humans.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gilson, M.K., Proteins Struct. Funct. Genet., 15(1993)266.

    Google Scholar 

  2. Wlodek, S.T., Antosiewicz, J., McCammon, J.A. and Gilson, M.K., In Pullman, A., Jortner, J. and Pullman, B. (Eds.) Modeling of Biomolecular Structures and Mechanisms, Kluwer, Dordrecht, 1995, pp. 25–37.

    Chapter  Google Scholar 

  3. Antosiewicz, J., McCammon, J.A. and Gilson, M.K., J. Mol. Biol., 238(1994)415.

    Google Scholar 

  4. Stites, W.E., Gittis, A.G., Lattman, E.E. and Shortie, D., J. Mol. Biol., 221(1991)7.

    Google Scholar 

  5. Dao-Pin, S., Anderson, D.E., Baase, W.A., Dahlquist, F.W. and Matthews, B.W., Biochemistry, 30(1991)11521.

    Google Scholar 

  6. Varadarajan, R., Lambright, D.G. and Boxer, S.G., Biochemistry, 28(1989)3771.

    Google Scholar 

  7. Bender, M.L., Clement, G.E., Kezdy, F.J. and Heck, H.d’A., J. Am. Chem. Soc., 86(1964)3680.

    Google Scholar 

  8. Fersht, A.R. and Sperling, J., J. Mol. Biol., 74(1973)137.

    Google Scholar 

  9. Martell, A.E. and Smith, R.M., Critical Stability Constants, Vols. l-IV, Plenum Press, New York, NY, 1974.

    Google Scholar 

  10. Antosiewicz, J., McCammon, J.A. and Gilson, M.K., Biochemistry, 35(1996)7819.

    Google Scholar 

  11. Wyman, J., J. Mol. Biol., 11(1965)631.

    Google Scholar 

  12. Schellman, J.A., Biopolymers, 14(1975)999.

    Google Scholar 

  13. Bashford, D. and Karplus, M., Biochemistry, 9(1990)327.

    Google Scholar 

  14. Mark, A.E. and van Gunsteren, W.F., J. Mol. Biol., 240(1994)167.

    Google Scholar 

  15. Boresch, S., Archontis, G. and Karplus, M., Proteins Struct. Funct. Genet., 20(1994)25.

    Google Scholar 

  16. Brady, G.P. and Sharp, K.A., J. Mol. Biol., 254(1995)77.

    Google Scholar 

  17. Kenneth, J. and Merz, M., J. Am. Chem. Soc., 113(1992)3572.

    Google Scholar 

  18. MacKerell, J.A.D., Sommer, M.S. and Karplus, M., J. Mol. Biol., 247(1995)774.

    Google Scholar 

  19. Lee, F.S. and Warshel, A., J. Chem. Phys., 97(1992)3100.

    Google Scholar 

  20. Levy, R.M., Belhadj, M. and Kitchen, D.B., J. Chem. Phys., 95(1991)3627.

    Google Scholar 

  21. Buono, G.S.D., Figueirido, F.E. and Levy, R.M., Proteins Struct. Funct. Genet., 20(1994)85.

    Google Scholar 

  22. McQuarrie, D.A., Statistical Mechanics, Harper and Row, New York, NY, 1973.

    Google Scholar 

  23. Urry, D.W., Peng, S.Q. and Parker, T.M., Biopolymers, 32(1992)373.

    Google Scholar 

  24. Urry, D.W., Peng, S.Q., Hayes, L., Jaggard, J. and Harris, R.D., Biopolymers, 30(1990)215.

    Google Scholar 

  25. Gilson, M.K., Curr. Opin. Struct. Biol., 5(1995)216.

    Google Scholar 

  26. Linderstrom-Lang, K., Compt. Rend. Tray. Lab. Carlsberg, 15(1924)7

    Google Scholar 

  27. Born, M., Z. Physik., 1(1920)45.

    Google Scholar 

  28. Tanford, C. and Kirkwood, J.G., J. Am. Chem. Soc., 79(1957)5333.

    Google Scholar 

  29. Tanford, C., J. Am. Chem. Soc., 79(1957)5340.

    Google Scholar 

  30. Shire, S.J., Hanania, G.I.H. and Gurd, F.R.N., Biochemistry, 13 (1974) 2967.

    Google Scholar 

  31. Imoto, T., Biophys. J., 44(1983)293.

    Google Scholar 

  32. Matthew, J.B., Gurd, F.R.N., Garie-Moreno, B.E., Flanagan, M.A., March, K.L. and Shire, S.J., Crit. Rev. Biochem., 18(1985)91.

    Google Scholar 

  33. Paul, C.H., J. Mol. Biol., 155(1982)53.

    Google Scholar 

  34. Gilson, M.K., Rashin, A.A., Fine, R. and Honig, B., J. Mol. Biol., 183(1985)503.

    Google Scholar 

  35. Warwicker, J. and Watson, H.C., J. Mol. Biol., 157(1982)671.

    Google Scholar 

  36. Klapper, I., Hagstrom, R., Fine, R., Sharp, K. and Honig, B., Proteins Struct. Funct. Genet., 1(1986)47.

    Google Scholar 

  37. Gilson, M.K. and Honig, B.H., Nature, 330(1987)84.

    Google Scholar 

  38. Sternberg, M.J., Hayes, F.R., Russell, A.J., Thomas, P.G. and Fersht, A.R., Nature, 330(1987)86.

    Google Scholar 

  39. Gilson, M.K. and Honig, B., Proteins Struct. Funct. Genet., 3(1988)32.

    Google Scholar 

  40. Gilson, M.K. and Honig, B., Proteins Struct. Funct. Genet., 4(1988)7.

    Google Scholar 

  41. Luty, B.A., Davis, M.E. and McCammon, J.A., J. Comput. Chem., 13(1992)768.

    Google Scholar 

  42. Richards, F.M., Annu. Rev. Biophys. Bioeng., 6(1977)151.

    Google Scholar 

  43. Bashford, D. and Gerwert, K., J. Mol. Biol., 224(1992)473.

    Google Scholar 

  44. Yang, A.-S., Gunner, M.R., Sampogna, R., Sharp, K. and Honig, B., Proteins Struct. Funct. Genet., 15(1993)252.

    Google Scholar 

  45. Antosiewicz, J., Briggs, J.M., Elcock, A.H., Gilson, M.K. and McCammon, J.A., J. Comput. Chem., 17 (1996) 1633.

    Google Scholar 

  46. Bashford, D. and Karplus, M., J. Phys. Chem., 95(1991)9556.

    Google Scholar 

  47. Karshikoff, A., Protein Eng., 8(1995)243.

    Google Scholar 

  48. Antosiewicz, J. and Porschke, D., Biochemistry, 28(1989)10072.

    Google Scholar 

  49. Beroza, P., Fredkin, D.R., Okamura, M.Y. and Feher, G., Proc. Natl. Acad. Sci. USA, 88(1991)5804.

    Google Scholar 

  50. Gilson, M.K. and Honig, B.H., Biopolymers, 25 (1986) 2097.

    Google Scholar 

  51. Simonson, T., Perahia, D. and Brunger, A.T., Biophys. J., 59(1991)670.

    Google Scholar 

  52. Simonson, T. and Perahia, D., Proc. Natl. Acad. Sci. USA, 92 (1995) 1082.

    Google Scholar 

  53. Nakamura, H., Sakamoto, T. and Wada, A., Protein Eng., 2(1988)177.

    Google Scholar 

  54. King, G., Lee, F.S. and Warshel, A., J. Chem. Phys., 95(1991)4366.

    Google Scholar 

  55. Smith, P.E., Brunne, R.M., Mark, A.E. and van Gunsteren, W.F., J. Phys. Chem., 97 (1993) 2009.

    Google Scholar 

  56. Lee, I. and Gilson, M.K., unpublished results.

    Google Scholar 

  57. Sitkoff, D., Sharp, K.A. and Honig, B., J. Phys. Chem., 98 (1994) 1978.

    Google Scholar 

  58. You, T.J. and Bashford, D., Biophys. J., 69 (1995) 1721.

    Google Scholar 

  59. Gilson, M.K., unpublished results.

    Google Scholar 

  60. Doctor, B.P., In Rein, R. and Golombek, A. (Eds.) Computer-Assisted Modeling of Receptor-Ligand Interactions. Theoretical Aspects and Applications to Drug Design, Vol. 289, Liss, New York, NY, 1989, pp. 305–316.

    Google Scholar 

  61. Gentry, M.K. and Doctor, B.P., In Massoulie, J., Bacou, F., Barnard, E., Chatonnet, A., Doctor, B.P. and Quinn, D.M. (Eds.) Cholinesterases: Structures, Function, Mechanism, Genetics and Cell Biology, American Chemical Society, Washington, DC, 1991, pp. 394–398.

    Google Scholar 

  62. Gibney, G., Camp, S., Dionne, M., MacPhee-Quigley, K. and Taylor, P., Proc. Natl. Acad. Sci. USA, 87(1990)7546.

    Google Scholar 

  63. Sussman, J.L., Harel, M., Frolow, F., Oefner, C., Goldman, A., Toker, L. and Silman, I., Science, 253(1991)872.

    Google Scholar 

  64. Radie, Z., Gibney, G., Kawamoto, S., MacPhee-Quigley, K., Bongiorno, C. and Taylor, P., Biochemistry, 31(1992)9760.

    Google Scholar 

  65. Tsukuda, H. and Blow, D.M., J. Mol. Biol., 184(1985)703.

    Google Scholar 

  66. Bernstein, F.C., Koetzle, T.F., Williams, T.F., Meyer Jr., G.J.B., Brice, M.D., Rodgers, J.R., Kennard, O., Shimanouchi, T. and Tasumi, M., J. Mol. Biol., 112(1977)535.

    Google Scholar 

  67. Rosenberry, T.L., Adv. Enzymol. Relat. Areas Mol. Biol., 43(1975)103.

    Google Scholar 

  68. Krupka, R.M., Biochemistry, 5 (1966) 1983.

    Google Scholar 

  69. Krupka, R.M., Biochemistry, 5 (1966) 1988.

    Google Scholar 

  70. Kossiakoff, A.A. and Spencer, S.A., Biochemistry, 20(1981)6462.

    Google Scholar 

  71. Harel, M., Schalk, I., Ehret-Sabatier, L., Bouet, F., Goeldner, M., Hirth, C., Axelsen, P., Silman, I. and Sussman, J.L., Proc. Natl. Acad. Sci. USA, 90(1993)9031.

    Google Scholar 

  72. Changeux, J.-P., Mol. Pharmacol., 2(1966)369.

    Google Scholar 

  73. Berman, H.A., Leonard, K. and Nowak, M.W., In Massoulie, J., Bacou, F., Barnard, E., Chatonnet, A., Doctor, B.P. and Quinn, D.M. (Eds.) Cholinesterases: Structures, Function, Mechanism, Genetics and Cell Biology, American Chemical Society, Washington, DC, 1991, pp. 229–234.

    Google Scholar 

  74. Kitz, R.J., Braswell, L.M. and Ginsberg, S., Mol. Pharmacol., 6(1969)108.

    Google Scholar 

  75. Yang, A.-S. and Honig, B., J. Mol. Biol., 231(1993)459.

    Google Scholar 

  76. Oliveberg, M., Arcus, V.L. and Fersht, A.R., Biochemistry, 34(1995)9424.

    Google Scholar 

  77. Tan, Y.-J., Oliveberg, M., Davis, B. and Fersht, A.R., J. Mol. Biol., 254(1995)980.

    Google Scholar 

  78. Robertson, A.D., unpublished results.

    Google Scholar 

  79. Nozaki, Y. and Tanford, C., J. Am. Chem. Soc., 89(1967)742.

    Google Scholar 

  80. Beroza, P. and Fredkin, D., J. Comput. Chem., 17 (1996) 1229.

    Google Scholar 

  81. Brunger, A.T. and Karplus, M., Proteins Struct. Funct. Genet., 4(1988)148.

    Google Scholar 

  82. Bass, M.B., Hopkins, D.F., Jaquysh, W.A.N. and Ornstein, R.L., Proteins Struct. Funct. Genet., 12(1992)266.

    Google Scholar 

  83. Bashford, D., Case, D.A., Dalvit, C., Tennant, L. and Wright, P.E., Biochemistry, 32(1993)8045.

    Google Scholar 

  84. Mehler, E.L., J. Phys. Chem., 100(1996)16006.

    Google Scholar 

  85. Ramanadham, M., Sieker, L.C. and Jensen, L.H., Acta Crystallogr., Sect. A, 37C(1981)33.

    Google Scholar 

  86. Diamond, R., J. Mol. Biol., 82(1974)371.

    Article  CAS  Google Scholar 

  87. Bartik, K., Redfield, C. and Dobson, C.M., Biophys. J., 66 (1994) 1180.

    Article  CAS  Google Scholar 

  88. Rico, M., Santoro, J., Gonzalez, C., Bruix, M. and Neira, J.L., In Cuchillo, C.M., de Llorens, R., Nogués, M.V. and Parés, X. (Eds.) Structure, Mechanism and Function of Ribonucleases, Proceedings of the 2nd International Meeting held in Sant Feliu de Guíxols, Girona, Spain, 1990, Bellaterra, Spain, 1991, pp. 9–14.

    Google Scholar 

  89. Antosiewicz, J., McCammon, J.A. and Gilson, M.K., Biochemistry, 35(1996)7819.

    Article  CAS  Google Scholar 

  90. Brown, L.R., Marco, A.D., Wagner, G. and Wüthrich, K., Eur. J. Biochem., 62(1976)103.

    Article  CAS  Google Scholar 

  91. Brown, L.R., Marco, A.D., Richarz, R., Wagner, G. and Wüthrich, K., Eur. J. Biochem., 88(1978)87.

    Article  CAS  Google Scholar 

  92. Richarz, R. and Wüthrich, K., Biochemistry, 17 (1978) 2263.

    Article  CAS  Google Scholar 

  93. Schaller, W. and Robertson, A.D., Biochemistry, 34(1995)4714.

    Article  CAS  Google Scholar 

  94. Swint-Kruse, L. and Robertson, A.D., Biochemistry, 34(1995)4724.

    Article  CAS  Google Scholar 

  95. Anderson, D.E., Becktel, W.J. and Dahlquist, F.W., Biochemistry, 29 (1990) 2403.

    Article  CAS  Google Scholar 

  96. Inagaki, F., Kawano, Y., Shimada, I., Takahashi, K. and Miyazawa, T., J. Biochem., 89 (1981) 1185.

    CAS  Google Scholar 

  97. Shirley, B.A., Stanssen, P., Steyaert, J. and Pace, C.N., J. Biol. Chem., 264(1989)11621.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Advanced Research in Biotechnology, National Institute of Standards and Technology, 9600 Gudelsky Drive, Rockville, MD, 20850-3479, USA

    Michael K. Gilson

Authors
  1. Michael K. Gilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH Zentrum, CH-8092, Zürich, Switzerland

    Wilfred F. van Gunsteren

  2. Amdyn Systems Inc., 28 Tower Street, 02143, Somerville, Massachusetts, USA

    Paul K. Weiner

  3. Zeneca Pharmaceuticals, Alderley Park, Macclesfied, SK10 4TG, Cheshire, UK

    Anthony J. Wilkinson

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Gilson, M.K. (1997). Modeling protonation equilibria in biomolecules. In: van Gunsteren, W.F., Weiner, P.K., Wilkinson, A.J. (eds) Computer Simulation of Biomolecular Systems. Computer Simulations of Biomolecular Systems, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1120-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-94-017-1120-3_7

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-8528-3

  • Online ISBN: 978-94-017-1120-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation