Protein Stability and Function

Theoretical Studies
  • J. Andrew McCammon
  • Chung F. Wong
  • Terry P. Lybrand


The convergence of several lines of development in chemistry and molecular biology has created major new needs and opportunities for theoretical studies of proteins. The traditional approaches of organic synthesis have been supplemented by methods for automated chemical synthesis and genetic engineering that allow the preparation of a wide variety of polypeptides, specifically altered enzymes, and other complex molecules. The choice of molecules to be synthesis for a given application is increasingly guided by structural information in addition to traditional methods such as chemical intuition and empirical correlation (quantitative structure-activity relationships, or QSAR). X-ray area detectors and new methods in NMR spectroscopy, combined with the improvements in our ability to synthesize and purify samples, are increasingly the rate at which high-resolution structures to proteins are becoming available.


Kcal Mole Protein Stability Free Energy Change Thermodynamic Cycle Relative Free Energy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahmad, F., and Bigelow, C. C., 1986, Estimation of the stability of globular proteins, Biopolymers 25:1623.CrossRefGoogle Scholar
  2. Baldwin, R. L., 1986, Seeding protein folding, Trends Biochem. Sci. 11:6.CrossRefGoogle Scholar
  3. Berendsen, H. J. C., 1985, Statistical mechanics and molecular dynamics: The calculation of free energy, in: Molecular Dynamics and Protein Structure (J. Hermans, ed.), University of North Carolina, Chapel Hill, pp. 43–46.Google Scholar
  4. Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., and Haak, J. R., 1984, Molecular dynamics with coupling to an external bath, J. Chem. Phys. 81:3684.CrossRefGoogle Scholar
  5. Berkowitz, M., and McCammon, J. A., 1982, Molecular dynamics with stochastic boundary conditions, Chem. Phys. Lett. 90:215.CrossRefGoogle Scholar
  6. Beveridge, D., and Mezei, M., 1985, Free energy simulations: The coupling parameter approach and topographical transition coordinates, in: Molecular Dynamics and Protein Structure (J. Hermans, ed.), University of North Carolina, Chapei Hill, pp. 53–57.Google Scholar
  7. Bode, W., and Schwager, P., 1975, The refined crystal structure of bovine ß-trypsin at 1.8 angstroms resolution, J. Mol. Biol. 98:693.PubMedCrossRefGoogle Scholar
  8. Brunger, A. T., Brooks, C. L., and Karplus, M., 1985, Active site dynamics of ribonuclease, Proc. Natl. Acad. Sci. U.S.A. 82:8458.PubMedCrossRefGoogle Scholar
  9. Cantor, C. R., and Schimmel, P. R., 1980, Biophysical Chemistry, W. H. Freeman, San Francisco.Google Scholar
  10. Craik, C. S., Largman, C., Fletcher, T., Roczniak, S., Barr, P. J., Fletterick, R., and Rutter, W. J., 1985, Redesigning trypsin: Alteration of substrate specificity, Science 228:291.PubMedCrossRefGoogle Scholar
  11. Friedman, H. L., 1985, A Course in Statistical Mechanics, Prentice-Hall, Englewood Cliffs, NJ.Google Scholar
  12. Hawkes, R., Grutter, M. G., and Schellman, J., 1984, Thermodynamic stability and point mutations of bacteriophage T4 lysozyme, J. Mol. Biol. 175:195.PubMedCrossRefGoogle Scholar
  13. Hermans, J., Berendsen, H. J. C., van Gunsteren, W. F., and Postma, J. P. M., 1984, A consistent empirical potential for water-protein interactions, Biopolymers 23:1513.CrossRefGoogle Scholar
  14. Hockney, R. N., and Eastwood, J. W., 1981, Computer Simulation Using Particles, McGraw-Hill, New York.Google Scholar
  15. Jorgensen, W. L., Chandrasekhar, J., Buckner, J. K., and Madura, J. D., 1986, Computer simulations of organic reactions in solution, Ann. N.Y. Acad. Sci. 482:198.PubMedCrossRefGoogle Scholar
  16. Lesk, A. M., and Chothia, C. H., 1986, The response or protein structures to amino-acid sequence changes, Phil. Trans. R. Soc. Lond. A317:345.CrossRefGoogle Scholar
  17. Lybrand, T. P., Ghosh, I., and McCammon, J. A., 1985, Hydration of chloride and bromide anions: Determination of relative free energy by computer simulation, J. Am. Chem. Soc. 107:7793.CrossRefGoogle Scholar
  18. Lybrand, T. P., McCammon, J. A., and Wipff, G., 1986, Theoretical calculation of relative binding affinity in host-guest systems, Proc. Natl. Acad. Sci. U.S.A. 83:833.PubMedCrossRefGoogle Scholar
  19. Lybrand, T. P., Lau, W. F., McCammon, J. A., and Pettitt, B. M., 1987, Molecular dynamics studies on antiviral agents: Thermodynamics of solvation and binding, in: Protein Structure and Design (D. Oxender, ed.), p. 227, Alan R.. Liss, New York.Google Scholar
  20. Madura, J. D., Pettitt, B. M., and McCammon, J. A., 1987, Geometric considerations in the calculation of relative free energies of activation, Chem. Phys. Lett. 140:83.CrossRefGoogle Scholar
  21. Mares-Guia, M., Nelson, D. L., and Rogana, E., 1977, Electronic effects in the interaction of para-substituted benzamidines with trypsin: The involvement of the π-electronic density at the central atom of the substituent in binding, J. Am. Chem. Soc. 99:2331.PubMedCrossRefGoogle Scholar
  22. McCammon, J. A., and Harvey, S. C., 1987, Dynamics of Proteins and Nucleic Acids, Cambridge University Press, Cambridge.Google Scholar
  23. McCammon, J. A., Karim, O. A., Lybrand, T. P., and Wong, C. F., 1986, Ionic association in water: From atoms to enzymes, Ann. N.Y. Acad. Sci. 482:210.PubMedCrossRefGoogle Scholar
  24. Pettitt, B. M., and Karplus, M., 1985, The potential of mean force surface for the alanine dipeptide in aqueous solution: A theoretical approach, Chem. Phys. Lett. 121: 194.CrossRefGoogle Scholar
  25. Postma, J. P. M., Berendsen, H. J. c., and Haak, J. R., 1982, Thermodynamics of cavity formation in water, Faraday Symp. Chem. Soc. 17:55.CrossRefGoogle Scholar
  26. Ryckaert, J. P., Ciccotti, G., and Berendsen, H. J. C., 1977, Numerical integration of Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes, J. Comp. Phys. 23:327.CrossRefGoogle Scholar
  27. Straatsma, T. P., Berendsen, H. J. C., and Postma, J. P. M., 1986, Free energy of hydrophobic hydration: A molecular dynamics study of noble gases in water, J. Chem. Phys. 85:6720.CrossRefGoogle Scholar
  28. Tembe, B. L., and McCammon, J. A., 1984, Ligand-receptor interactions, Comput. Chem. 8:281.CrossRefGoogle Scholar
  29. Van Holde, K. E., 1971, Physical Biochemistry, Prentice-Hall, Englewood Cliffs, N.J.Google Scholar
  30. Weiner, P. K., and Kollman, P. A., 1981, AMBER: Assisted model building with energy refinement. A general program for modeling molecules and their interactions, J. Comput. Chem. 2:287.CrossRefGoogle Scholar
  31. Wong, C. F., and McCammon, J. A., 1986a, Dynamics and design of enzymes and inhibitors, J. Am. Chem. Soc. 108:3830.CrossRefGoogle Scholar
  32. Wong, C. F., and McCammon, J. A., 1986b, Computer simulation and the design of new biological molecules, Isr. J. Chem. 27:211.Google Scholar
  33. Wong, C. F., and McCammon, J. A., 1987, Thermodynamics of enzyme folding and activity: Theory and experiment, in: Structure, Dynamics and Function of Biomolecules (A. Ehrenberg and R. Rigler, eds.), Springer-Verlag, Berlin, pp. 51–55.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • J. Andrew McCammon
    • 1
  • Chung F. Wong
    • 1
  • Terry P. Lybrand
    • 1
  1. 1.Department of ChemistryUniversity of HoustonHoustonUSA

Personalised recommendations