Skip to main content
SpringerLink
Log in

Microcalorimetry of Macromolecules: The Physical Basis of Biological Structures

  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

This manuscript focuses on a specialized field within solution thermodynamics that encompasses some of the major macromolecular components comprising all biological systems. Nucleic acids and proteins are large biomolecules that represent quazi-macroscopic systems with highly ordered structures in which each atom occupies a defined space. In view of their unique quaternary structures that resemble aperiodic crystals, one might reasonably surmise that the resultant solution thermodynamics are highly specific. Systematic investigations of these biological macromolecules have necessitated the development of ultrasensitive measurement techniques including differential scanning and isothermal titration calorimetry. These experimental approaches represent the gold standard in terms of microcalorimetric instrumentation designed to characterize complex macromolecular systems. This paper presents an overview of thermodynamic data gleaned from studies employing these calorimetric techniques as part of our comprehensive strategy to characterize the energetic basis of nucleic acid and protein stability.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19
Fig. 20

Similar content being viewed by others

References

  1. Hooke, R.: Micrographia, or, Some Physiological Descriptions of Minute Bodies Made by Magnifying Glasses with Observations and Inquiries Thereupon. J. Martyn and J. Allestry, London (1665)

    Book  Google Scholar 

  2. Schrödinger, E.: What is Life?. Cambridge University Press, Cambridge (1944)

    Google Scholar 

  3. Miescher, F.: Ueber die chemische zusammensetzung der eiterzellen. Medicinisch-chemische Untersuchungen 4, 441–460 (1871)

    Google Scholar 

  4. Avery, O.T., Macleod, C.M., McCarty, M.: Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Induction of transformation by a deoxyribonucleic acid fraction isolated from pnemococcus type III. J. Exp. Med. 79, 137–157 (1944)

    Article  CAS  Google Scholar 

  5. Chargaff, E.: Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia 6, 201–240 (1950)

    Article  Google Scholar 

  6. Watson, J.D., Crick, F.H.: Molecular structure of nucleic acids. Nature 171, 737–738 (1953)

    Article  CAS  Google Scholar 

  7. Marmur, J., Doty, P.: Determination of the base composition of deoxyribonucleic acid from its thermal melting temperature. J. Mol. Biol. 5, 109–118 (1962)

    Article  CAS  Google Scholar 

  8. Kendrew, J.C., Bodo, G., Dintzis, H.M., Parrish, R.G., Wyckoff, H., Phillips, D.C.: A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181, 662–666 (1958)

    Article  CAS  Google Scholar 

  9. Anfinsen, C.B.: The limited digestion of ribonuclease with pepsin. J. Biol. Chem. 221, 405–412 (1956)

    CAS  Google Scholar 

  10. Privalov, P.L., Monaselidze, D.R., Mrevlishvili, G.M., Magaldadze, V.A.: Heat of intramolecular fusion of macromolecules. Sov. Phys. JETP 20, 1393–1396 (1965)

    Google Scholar 

  11. Privalov, P.L.: Scanning microcalorimeters for studying macromolecules. Pure Appl. Chem. 52, 479–497 (1980)

    Article  CAS  Google Scholar 

  12. Privalov, P.L., Griko, Y.V., Venyaminov, S.Y., Kutyshenko, V.P.: Cold denaturation of myoglobin. J. Mol. Biol. 190, 487–498 (1986)

    Article  CAS  Google Scholar 

  13. Privalov, P.L., Plotnikov, V.V.: Three generations of scanning microcalorimeters for liquids. Thermochim. Acta 139, 257–277 (1989)

    Article  CAS  Google Scholar 

  14. McKinnon, I.R., Fall, L., Parody-Morreale, A., Gill, S.J.: A twin titration microcalorimeter for the study of biochemical reactions. Anal. Biochem. 139, 134–139 (1984)

    Article  CAS  Google Scholar 

  15. Privalov, P.L., Mrevlishvili, G.M.: Hydration of macromolecules in native and denatured states (in Russian). Biofizika 12, 22–29 (1967)

    CAS  Google Scholar 

  16. Privalov, P.L.: Water and its role in biological systems (in Russian). Biofizika 13, 163–177 (1968)

    CAS  Google Scholar 

  17. Privalov, P.L., Ptitsyn, O.B., Birshtein, T.M.: Determination of stability of DNA double helix in an aqueous media. Biopolymers 8, 559–571 (1969)

    Article  CAS  Google Scholar 

  18. Watson, J.D., Crick, F.H.: The structure of DNA. Cold Spring Harbor Symp. Quant. Biol. 18, 123–131 (1953)

    Article  CAS  Google Scholar 

  19. Breslauer, K.J., Sturtevant, J.M., Tinoco Jr, I.: Calorimetric and spectroscopic investigation of the helix-to-coil transition of a ribo-oligonucleotide: rA7U7. J. Mol. Biol. 99, 549–565 (1975)

    Article  CAS  Google Scholar 

  20. Breslauer, K.J., Sturtevant, J.M.: A calorimetric investigation of single stranded base stacking in the ribo-oligonucleotide a7. Biophys. Chem. 7, 205–209 (1977)

    Article  CAS  Google Scholar 

  21. Remeta, D.P., Senior, M.M., Gaffney, B.L., Jones, R.A., Breslauer, K.J.: Effect of DNA-base composition and sequence on the binding-affinity of daunomycin. Biophys. J. 47, A335 (1985)

    Google Scholar 

  22. Breslauer, K.J., Frank, R., Blocker, H., Marky, L.A.: Predicting DNA duplex stability from the base sequence. Proc Natl Acad Sci USA 83, 3746–3750 (1986)

    Article  CAS  Google Scholar 

  23. Remeta, D.P., Mudd, C.P., Berger, R.L., Breslauer, K.J.: Application of stopped-flow microcalorimetry for the determination of daunomycin–deoxypolynucleotide binding enthalpies. Biophys. J. 53, A480 (1988)

    Google Scholar 

  24. Breslauer, K.J., Remeta, D.P., Chou, W.Y., Ferrante, R., Curry, J., Zaunczkowski, D., Snyder, J.G., Marky, L.A.: Enthalpy entropy compensations in drug DNA-binding studies. Proc. Natl. Acad. Sci. USA 84, 8922–8926 (1987)

    Article  CAS  Google Scholar 

  25. SantaLucia, J.: A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. Proc. Natl. Acad. Sci. USA 95, 1460–1465 (1998)

    Article  CAS  Google Scholar 

  26. Privalov, P.L.: Microcalorimetry of Macromolecules: The Physical Basis of Biological Structures, vol. 16. Wiley, Hoboken (2012)

    Book  Google Scholar 

  27. Minetti, C.A., Privalov, P.L., Remeta, D.P.: Calorimetric methods to characterize the forces driving macromolecular association and folding processes. Proteins in Solution and at Interfaces: Methods and Applications in Biotechnology and Materials Science, pp. 139–177. Wiley, Hoboken (2013)

    Chapter  Google Scholar 

  28. Jelesarov, I., Crane-Robinson, C., Privalov, P.L.: The energetics of HMG box interactions with DNA: thermodynamic description of the target DNA duplexes. J. Mol. Biol. 294, 981–995 (1999)

    Article  CAS  Google Scholar 

  29. Chalikian, T.V., Volker, J., Plum, G.E., Breslauer, K.J.: A more unified picture for the thermodynamics of nucleic acid duplex melting: A characterization by calorimetric and volumetric techniques. Proc. Natl. Acad. Sci. USA 96, 7853–7858 (1999)

    Article  CAS  Google Scholar 

  30. Holbrook, J.A., Capp, M.W., Saecker, R.M., Record, M.T.: Enthalpy and heat capacity changes for formation of an oligomeric DNA duplex: interpretation in terms of coupled processes of formation and association of single-stranded helices. Biochemistry 38, 8409–8422 (1999)

    Article  CAS  Google Scholar 

  31. Rouzina, I., Bloomfield, V.A.: Heat capacity effects on the melting of DNA. 1. General aspects. Biophys. J. 77, 3242–3251 (1999)

    Article  CAS  Google Scholar 

  32. Rouzina, I., Bloomfield, V.A.: Heat capacity effects on the melting of DNA. 2. Analysis of nearest-neighbor base pair effects. Biophys. J. 77, 3252–3255 (1999)

    Article  CAS  Google Scholar 

  33. Ross, P.D., Howard, F.B.: The thermodynamic contribution of the 5-methyl group of thymine in the two- and three-stranded complexes formed by poly(du) and poly(dt) with poly(da). Biopolymers 68, 210–222 (2003)

    Article  CAS  Google Scholar 

  34. Tikhomirova, A., Taulier, N., Chalikian, T.V.: Energetics of nucleic acid stability: the effect of ∆c p . J. Am. Chem. Soc. 126, 16387–16394 (2004)

    Article  CAS  Google Scholar 

  35. Privalov, P.L., Potekhin, S.A.: Scanning microcalorimetry in studying temperature induced changes in proteins. Methods Enzymol. 131, 4–51 (1986)

    CAS  Google Scholar 

  36. Privalov, G.P., Privalov, P.L.: Problems and prospects in microcalorimetry of biological macromolecules. Methods Enzymol. 323, 31–62 (2000)

    CAS  Google Scholar 

  37. Breslauer, K.J., Freire, E., Straume, M.: Calorimetry—a tool for DNA and ligand–DNA studies. Methods Enzymol. 211, 533–567 (1992)

    CAS  Google Scholar 

  38. Vesnaver, G., Breslauer, K.J.: The contribution of DNA single-stranded order to the thermodynamics of duplex formation. Proc. Natl. Acad. Sci. USA 88, 3569–3573 (1991)

    Article  CAS  Google Scholar 

  39. Privalov, P.L., Jelesarov, I., Read, C.M., Dragan, A.I., Crane-Robinson, C.: The energetics of HMG box interactions with DNA: thermodynamics of the DNA binding of the HMG box from mouse sox-5. J. Mol. Biol. 294, 997–1013 (1999)

    Article  CAS  Google Scholar 

  40. Dragan, A.I., Frank, L., Liu, Y.Y., Makeyeva, E.N., Crane-Robinson, C., Privalov, P.L.: Thermodynamic signature of GCN4-bZIP binding to DNA indicates the role of water in discriminating between the ap-1 and atf/creb sites. J. Mol. Biol. 343, 865–878 (2004)

    Article  CAS  Google Scholar 

  41. Dragan, A.I., Liu, Y.Y., Makeyeva, E.N., Privalov, P.L.: DNA-binding domain of GCN4 induces bending of both the atf/creb and ap-1 binding sites of DNA. Nucleic Acids Res. 32, 5192–5197 (2004)

    Article  CAS  Google Scholar 

  42. Dragan, A.I., Read, C.M., Makeyeva, E.N., Milgotina, E.I., Crane-Robinson, C., Privalov, P.L.: DNA binding and bending by sequence specific HMG boxes: energetic determinants of specificity. Biophys. J. 86, 371–393 (2004)

    Article  Google Scholar 

  43. Crane-Robinson, C., Dragan, A.I., Privalov, P.L.: The extended arms of DNA-binding domains: a tale of tails. Trends Biochem. Sci. 31, 547–552 (2006)

    Article  CAS  Google Scholar 

  44. Dragan, A.I., Li, Z.L., Makeyeva, E.N., Milgotina, E.I., Liu, Y.Y., Crane-Robinson, C., Privalov, P.L.: Forces driving the binding of homeodomains to DNA. Biochemistry 45, 141–151 (2006)

    Article  CAS  Google Scholar 

  45. Dragan, A.I., Liggins, J.R., Crane-Robinson, C., Privalov, P.L.: The energetics of specific binding of at-hooks from HMGA1 to target DNA (vol. 327, p. 393, 2003). J. Mol. Biol. 362, 876 (2006)

    Article  CAS  Google Scholar 

  46. Privalov, P.L., Dragan, A.I., Crane-Robinson, C., Breslauer, K.J., Remeta, D.P., Minetti, C.A.S.A.: What drives proteins into the major or minor grooves of DNA? J. Mol. Biol. 365, 1–9 (2007)

    Article  CAS  Google Scholar 

  47. Carrillo, R.J., Dragan, A.I., Privalov, P.L.: Stability and DNA-binding ability of the bZIP dimers formed by the atf-2 and c-jun transcription factors. J. Mol. Biol. 396, 431–440 (2010)

    Article  CAS  Google Scholar 

  48. Privalov, P.L., Dragan, A.I., Crane-Robinson, C.: Interpreting protein/DNA interactions: Distinguishing specific from non-specific and electrostatic from non-electrostatic components. Nucleic Acids Res. 39, 2483–2491 (2011)

    Article  CAS  Google Scholar 

  49. Vesnaver, G., Chang, C.N., Eisenberg, M., Grollman, A.P., Breslauer, K.J.: Influence of abasic and anucleosidic sites on the stability, conformation, and melting behavior of a DNA duplex—correlations of thermodynamic and structural data. Proc. Natl. Acad. Sci. USA 86, 3614–3618 (1989)

    Article  CAS  Google Scholar 

  50. Plum, G.E., Grollman, A.P., Johnson, F., Breslauer, K.J.: Influence of the oxidatively damaged adduct 8-oxodeoxyguanosine on the conformation, energetics, and thermodynamic stability of a DNA duplex. Biochemistry 34, 16148–16160 (1995)

    Article  CAS  Google Scholar 

  51. Gelfand, C.A., Plum, G.E., Grollman, A.P., Johnson, F., Breslauer, K.J.: Thermodynamic consequences of an abasic lesion in duplex DNA are strongly dependent on base sequence. Biochemistry 37, 7321–7327 (1998)

    Article  CAS  Google Scholar 

  52. Minetti, C.A.S.A., Remeta, D.P., Zharkov, D.O., Plum, G.E., Johnson, F., Grollman, A.P., Breslauer, K.J.: Energetics of lesion recognition by a DNA repair protein: thermodynamic characterization of formamidopyrimidine–glycosylase (Fpg) interactions with damaged DNA duplexes. J. Mol. Biol. 328, 1047–1060 (2003)

    Article  CAS  Google Scholar 

  53. Minetti, C., Remeta, D.P., Breslauer, K.J.: A continuous hyperchromicity assay to characterize the kinetics and thermodynamics of DNA lesion recognition and base excision. Proc. Natl. Acad. Sci. USA 105, 70–75 (2008)

    Article  CAS  Google Scholar 

  54. Minetti, C.A.S.A., Remeta, D.P., Dickstein, R., Breslauer, K.J.: Energetic signatures of single base bulges: thermodynamic consequences and biological implications. Nucleic Acids Res. 38, 97–116 (2010)

    Article  CAS  Google Scholar 

  55. Minetti, C.A.S.A., Remeta, D.P., Johnson, F., Iden, C.R., Breslauer, K.J.: Impact of alpha-hydroxy-propanodeoxyguanine adducts on DNA duplex energetics: opposite base modulation and implications for mutagenicity and genotoxicity. Biopolymers 93, 370–382 (2010)

    CAS  Google Scholar 

  56. Lukin, M., Minetti, C., Remeta, D.P., Attaluri, S., Johnson, F., Breslauer, K.J., de los Santos, C.: Novel post-synthetic generation, isomeric resolution, and characterization of fapy-dg within oligodeoxynucleotides: differential anomeric impacts on DNA duplex properties. Nucleic Acids Res 39, 5776–5789 (2011)

    Article  CAS  Google Scholar 

  57. Privalov, P.L.: Cold denaturation of proteins. Crit. Rev. Biochem. Mol. 25, 281–306 (1990)

    Article  CAS  Google Scholar 

  58. Griko, Y.V., Privalov, P.L., Sturtevant, J.M., Venyaminov, S.Y.: Cold denaturation of staphylococcal nuclease. Proc. Natl. Acad. Sci. USA 85, 3343–3347 (1988)

    Article  CAS  Google Scholar 

  59. Griko, Y.V., Venyaminov, S.Y., Privalov, P.L.: Heat and cold denaturation of phosphoglycerate kinase (interaction of domains). FEBS Lett. 244, 276–278 (1989)

    Article  CAS  Google Scholar 

  60. Gill, S., Wadsö, I.: An equation of state describing hydrophobic interactions. Proc. Natl. Acad. Sci. USA 73, 2955–2958 (1976)

    Article  CAS  Google Scholar 

  61. Kauzmann, W.: Some factors in the interpretation of protein denaturation. Adv. Prot. Chem. 14, 1–63 (1959)

    CAS  Google Scholar 

  62. Sturtevant, J.M.: Heat capacity and entropy changes in processes involving proteins. Proc. Natl. Acad. Sci. USA 74, 2236–2240 (1977)

    Article  CAS  Google Scholar 

  63. Wilhelm, E.: What you always wanted to know about heat capacities, but were afraid to ask. J. Solution Chem. 39, 1777–1818 (2010)

    Article  CAS  Google Scholar 

  64. Hvidt, A., Westh, P.: Different views on the stability of protein conformations and hydrophobic effects. J. Solution Chem. 27, 395–402 (1998)

    Article  CAS  Google Scholar 

  65. Privalov, P.L., Gill, S.J.: Stability of protein-structure and hydrophobic interaction. Adv. Protein Chem. 39, 191–234 (1988)

    CAS  Google Scholar 

  66. Privalov, P.L.: Stability of proteins. Small globular proteins. Adv. Protein Chem. 33, 167–241 (1979)

    CAS  Google Scholar 

  67. Novokhatny, V.V., Kudinov, S.A., Privalov, P.L.: Domains in human-plasminogen. J. Mol. Bio. 179, 215–232 (1984)

    Article  CAS  Google Scholar 

  68. Rich, A., Crick, F.H.: The structure of collagen. Nature 176, 915–916 (1955)

    Article  CAS  Google Scholar 

  69. Ramachandran, G., Kartha, G.: Structure of collagen. Nature 176, 593–595 (1955)

    Article  CAS  Google Scholar 

  70. Bella, J., Brodsky, B., Berman, H.M.: Hydration structure of a collagen peptide. Structure 3, 893–906 (1995)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, The Johns Hopkins University, Baltimore, MD, 21218, USA

    Peter L. Privalov

Authors
  1. Peter L. Privalov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter L. Privalov.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Privalov, P.L. Microcalorimetry of Macromolecules: The Physical Basis of Biological Structures. J Solution Chem 44, 1141–1161 (2015). https://doi.org/10.1007/s10953-015-0337-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-015-0337-x

Keywords

Search

Navigation