An empirical approach to protein conformation stability and flexibility

Experimental measurements of disulfide bond stability at various stages of protein folding are considered in terms of the effective concentrations of the thiol groups relative to each other; values of up to 107M are observed, so that intramolecular interactions within the interior of a protein are much more stable, and provide greater stability to the folded conformation, than those on the surface or in a flexible segment. Intramolecular interactions can have substantially lower free energies than intermolecular, for solely entropic reasons; this implies that polar interactions, such as hydrogen bonds and salt bridges, can provide net stabilization to a folded conformation, in spite of the unfolded protein having intermolecular interactions with the solvent. These considerations can account for the lower free energy and enthalpy of the folded state and are useful for considering protein flexibility.

[1]  A. Kossiakoff.  Protein dynamics investigated by the neutron diffraction–hydrogen exchange technique , 1982, Nature.

[2]  L. Mandolini,et al.  Ring closure reactions of bifunctional chain molecules , 1981 .

[3]  A. J. Kirby,et al.  Effective Molarities for Intramolecular Reactions , 1980 .

[4]  K. Wüthrich,et al.  Structural interpretation of the amide proton exchange in the basic pancreatic trypsin inhibitor and related proteins. , 1979, Journal of molecular biology.

[5]  D. Phillips,et al.  Crystallographic studies of the dynamic properties of lysozyme , 1979, Nature.

[6]  Hans Frauenfelder,et al.  Temperature-dependent X-ray diffraction as a probe of protein structural dynamics , 1979, Nature.

[7]  K. Wüthrich,et al.  Kinetics of the exchange of individual amide protons in the basic pancreatic trypsin inhibitor. , 1979, Journal of molecular biology.

[8]  R. Mayer,et al.  Side chain–backbone hydrogen bonds in peptides containing glutamic acid residues , 1979 .

[9]  P. Privalov.  Stability of proteins: small globular proteins. , 1979, Advances in protein chemistry.

[10]  K. Wüthrich,et al.  Characterisation of a local structure in the synthetic parathyroid hormone fragment 1--34 by 1H nuclear-magnetic-resonance techniques. , 1978, European journal of biochemistry.

[11]  M. Perutz.  Electrostatic effects in proteins. , 1978, Science.

[12]  K. Wüthrich,et al.  Dynamic model of globular protein conformations based on NMR studies in solution , 1978, Nature.

[13]  T. Creighton,et al.  Immunochemical analysis of the conformational properties of intermediates trapped in the folding and unfolding of bovine pancreatic trypsin inhibitor. , 1978, Journal of molecular biology.

[14]  K Wüthrich,et al.  The influence of a single salt bridge on static and dynamic features of the globular solution conformation of the basic pancreatic trypsin inhibitor. 1H and 13C nuclear-magnetic-resonance studies of the native and the transaminated inhibitor. , 1978, European journal of biochemistry.

[15]  L. Sieker,et al.  Water structure in a protein crystal: rubredoxin at 1.2 A resolution. , 1978, Journal of molecular biology.

[16]  T. Creighton,et al.  Experimental studies of protein folding and unfolding. , 1978, Progress in biophysics and molecular biology.

[17]  J. Bello.  Stability of protein conformation: internal packing and enthalpy of fusion of model compounds. , 1977, Journal of theoretical biology.

[18]  M. Page.  Entropy, Binding Energy, and Enzymic Catalysis† , 1977 .

[19]  T. Creighton,et al.  Energetics of folding and unfolding of pancreatic trypsin inhibitor. , 1977, Journal of molecular biology.

[20]  T. Creighton.  Effects of urea and guanidine-HCl on the folding and unfolding of pancreatic trypsin inhibitor. , 1977, Journal of molecular biology.

[21]  Paul Haake,et al.  Equilibrium constants for association of guanidinium and ammonium ions with oxyanions: The effect of changing basicity of the oxyanion , 1977 .

[22]  S. Leach,et al.  Immunological measurements of conformational motility in regions of the myoglobin molecule. , 1977, Biochemistry.

[23]  A. Cooper,et al.  Thermodynamic fluctuations in protein molecules. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Janin,et al.  Surface area of globular proteins. , 1976, Journal of molecular biology.

[25]  P. Privalov,et al.  Thermodynamic investigations of proteins. III. Thermodynamic description of lysozyme. , 1976, Biophysical chemistry.

[26]  H. Edelhoch,et al.  The thermodynamic basis of the stability of proteins, nucleic acids, and membranes. , 1976, Advances in protein chemistry.

[27]  K. Wüthrich,et al.  Preferred spatial arrangement of the aromatic side chains in linear oligopeptides containing tyrosine. , 1976, Helvetica chimica acta.

[28]  D Eagland,et al.  The role of solvent interactions in protein conformation. , 1975, CRC critical reviews in biochemistry.

[29]  P. Privalov,et al.  A thermodynamic approach to the problem of stabilization of globular protein structure: a calorimetric study. , 1974, Journal of molecular biology.

[30]  C. Chothia,et al.  Hydrophobic bonding and accessible surface area in proteins , 1974, Nature.

[31]  M. Levitt,et al.  Energy refinement of hen egg-white lysozyme. , 1974, Journal of molecular biology.

[32]  C B Anfinsen,et al.  An immunologic approach to the conformational equilibria of polypeptides. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[33]  A. Fersht,et al.  Conformational equilibria in -and -chymotrypsin. The energetics and importance of the salt bridge. , 1972, Journal of molecular biology.

[34]  W. Jencks,et al.  Entropic contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[35]  H. Morawetz,et al.  Derivation of the Ring Closure Probability from the Distribution of Reaction Products when Reagents of the Type X(CH2)nY Undergo Simultaneous Cyclization and Polycondensation , 1970 .

[36]  S. N. Timasheff.  Protein-solvent interactions and protein conformation , 1970 .

[37]  I. M. Klotz,et al.  Stability of an amide-hydrogen bond in an apolar environment. , 1968, Biochemistry.

[38]  C. Tanford.  Protein denaturation. , 1968, Advances in protein chemistry.

[39]  J. S. Ard,et al.  NEAR INFRARED INVESTIGATION OF INTERAMIDE HYDROGEN BONDING IN AQUEOUS SOLUTION. , 1964, The Journal of biological chemistry.

[40]  W. Cleland.  DITHIOTHREITOL, A NEW PROTECTIVE REAGENT FOR SH GROUPS. , 1964, Biochemistry.

[41]  C. Tanford.  Contribution of Hydrophobic Interactions to the Stability of the Globular Conformation of Proteins , 1962 .

[42]  I. M. Klotz,et al.  Hydrogen Bonds between Model Peptide Groups in Solution , 1962 .

[43]  W. Kauzmann.  Some factors in the interpretation of protein denaturation. , 1959, Advances in protein chemistry.

[44]  H. Jaffe.  Inter- and Intramolecular Hydrogen Bonds1 , 1957 .

[45]  C. Tanford.  The Association of Acetate with Ammonium and Guanidinium Ions , 1954 .

[46]  R. Gurney.  Ionic processes in solution , 1953 .

[47]  S. Lifson,et al.  Hydrogen Bonding and Ionization of Carboxylic Acids in Aqueous Solutions , 1951 .