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An analysis of packing in the protein folding problem

Published online by Cambridge University Press:  17 March 2009

Frederic M. Richards  and
Wendell A. Lim
Frederic M. Richards
Affiliation:
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06437USA
Wendell A. Lim
Affiliation:
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06437USA
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Extract

The number of globular proteins for which high resolution structures are available is rapidly increasing. In each case the particular sequence of the polypeptide appears to yield only a single, compact, biologically active structure. However, peptides with no obvious sequence similarity may form remarkably similar structures.

Type
Research Article
Information
Quarterly Reviews of Biophysics , Volume 26 , Issue 4 , November 1993 , pp. 423 - 498
Copyright
Copyright © Cambridge University Press 1993

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References

Ansari, A., Berendzen, J., Bowne, S. F., Frauenfelder, H., Iben, I. E. T., Sauke, T. B., Shyamsunder, E. & Young, R. D. (1985). Protein states and protein quakes. Proc. Natl. Acad. Sci. U.S.A. 82, 5000–5004.CrossRefGoogle Scholar
Baldwin, R. L. (1986). Temperature dependence of the hydrophobic interaction in protein folding. Proc. Natl. Acad. Sci. U.S.A., 83, 8069–8072.CrossRefGoogle ScholarPubMed
Bashford, D., Chothia, C. & Lesk, A. M. (1987). Determination of a protein fold: unique features of the globin amino acid sequences. J. Mol. Biol. 196, 199–216.CrossRefGoogle ScholarPubMed
Behe, M. J., Lattman, E. E. & Rose, G. D. (1991). The protein-folding problem: The native fold determines packing, but does packing determine the native fold? Proc. Natl. Acad. Si. U.S.A. 88, 4195–4199.CrossRefGoogle ScholarPubMed
Benedetti, E., Morelli, G., Nemethy, G. & Scheraga, H. A. (1983). Statistical and energetic analysis of side-chain conformations in oligopeptides. Int. J. Pept Protein Res. 22, 1–15.CrossRefGoogle ScholarPubMed
Billeter, M. (1992). Comparison of protein structures determined by NMR in solution and by X-ray diffraction in single crystals. Q. Rev. Biophys. 25, 325–376.CrossRefGoogle ScholarPubMed
Bowie, J. U. & Sauer, R. T. (1989). Identifying determinants of folding and activity for a protein of unknown structure. Proc. Natl. Acad. Sci. U.S.A. 86, 2152–2156.CrossRefGoogle ScholarPubMed
Bowie, J. U., Reidhaar-Olson, J. F., Lim, W. A. & Sauer, R. T. (1990). Deciphering the message in protein sequences: Tolerance to amino acid substitutions. Science 247, 1306–1310.CrossRefGoogle ScholarPubMed
Bowie, J. U., Lüthy, R. & Eisenberg, D. (1991). A method to identifying protein sequences that fold into a known three-dimensional structure. Science, N. Y. 253, 164–170.CrossRefGoogle ScholarPubMed
Chan, H. S. & Dill, K. A. (1989 a). Intrachain loops in polymers: Effects of excluded volume. J. Chem. Phys. 90, 492–509.CrossRefGoogle Scholar
Chan, H. S. & Dill, K. A. (1989 b). Compact polymers. Macromolecules 22, 4559–4573.CrossRefGoogle Scholar
Chan, H. S. & Dill, K. A. (1990). Origins of structure in globular proteins. Proc. Natl. Acad. Si. U.S.A. 87, 6388–6392.CrossRefGoogle ScholarPubMed
Chan, H. S. & Dill, K. A. (1991). Polymer principles in protein structure and stability. Annu. Rev. Biophys. Biophys. Chem. 20, 447–490.CrossRefGoogle ScholarPubMed
Chandler, D., Weeks, J. D. & Anderson, H. C. (1983). Van der Waals picture of liquids, solids, and phase transformations. Science, N. Y. 220, 787–794.CrossRefGoogle Scholar
Chothia, C. (1975). Structural invariants in protein folding. Nature, Lond. 254, 304–308.CrossRefGoogle ScholarPubMed
Chothia, C. & Lesk, A. M. (1979). Protein evolution and helix packing in globins. In Protein Folding (ed. Balaban, M. and Jaenicke, R.). North Holland: Elsevier.Google Scholar
Chothia, C. & Lesk, A. M. (1987). The evolution of protein structures. Cold Spring Harbor Symp. Quant. Biol. 52, 399–405.CrossRefGoogle Scholar
Connelly, P. R., Varadarajan, R., Sturtevant, J. M. & Richards, F. M. (1990). Thermodynamics of protein-peptide interactions in the ribonuclease S system studies by titration calorimetry. Biochemistry 29, 6108–6114.CrossRefGoogle ScholarPubMed
Connolly, M. L. (1986). Atomic size packing defects in proteins. Int. J. Peptide Protein Res. 28, 360–363.CrossRefGoogle ScholarPubMed
Dao-Pin, S., Alber, T., Baase, W. A., Wozniak, J. A. & Matthews, B. W. (1991 a). Structural and thermodynamic analysis of the packing of two α-helices in bacteriophage T4 lysozyme. J. Mol. Biol. 221, 647–667.CrossRefGoogle Scholar
Dao-Pin, S., Anderson, D. E., Baase, W. A., Dahlquist, F. W. & Matthews, B. W. (1991 b). Structural and thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme. Biochemistry 30, 11521–11529.CrossRefGoogle ScholarPubMed
Dickerson, R. E. (March, 1980). Cytochrome C and the evolution of energy metabolism. Sci. Am. 242, 136–153.CrossRefGoogle ScholarPubMed
Dill, K. A. (1990 a). Dominant forces in protein folding. Biochemistry 29, 7133–7155.CrossRefGoogle ScholarPubMed
Dill, K. A. and response by Privalov, P. L., Gill, S. J. & Murphy, K. P. (1990 b). The meaning of hydrophobicity. Science, N. Y. 250, 297–298.CrossRefGoogle ScholarPubMed
Dill, K. A. & Shortle, D. (1991). Denatured states of proteins. Annu. Rev. Biochem. 60, 795–825.CrossRefGoogle ScholarPubMed
Drexler, K. E. (1981). Molecular engineering: An approach to the development of general capabilities for molecular manipulation. Proc. Natl. Acad. Sci. U.S.A. 78, 5275–5278.CrossRefGoogle Scholar
Dunbrack, R. L. & Karplus, M. (1993). A backbone dependent rotamer library for proteins: Application to sidechain prediction. J. Mol. Biol. 230, 543–574.CrossRefGoogle ScholarPubMed
Eigenbrot, C., Randal, M. & Kossiakoff, A. A. (1990). Structural effects induced by removal of a disulfide-bridge: the X-ray structure of the C30A/C51A mutant of basic pancreatic trypsin inhibitor of 1·6 Å. Protein Engineering 3, 591–598.CrossRefGoogle ScholarPubMed
Engh, R. A. & Huber, R. (1991). Accurate bond and angle parameters for X-ray structure refinement. Acta Crystallogr. A47, 392–400.CrossRefGoogle Scholar
Eriksson, A. E., Baase, W. A., Wozniak, J. A. & Matthews, B. W. (1992 a). A cavity-containing mutant of T4 lysozyme is stabilized by buried benzene. Nature, Lond. 355, 371–373.CrossRefGoogle ScholarPubMed
Eriksson, A. E., Baase, W. A., Zhang, X. -J., Heinz, D. W., Blaber, M., Baldwin, E. P. & Matthews, B. W. (1992 b). Response of a protein structure to cavity-creating mutations and its relationship to the hydrophobic effect. Science, N. Y. 255, 178–183.CrossRefGoogle ScholarPubMed
Eriksson, A. E., Baase, W. A. & Matthews, B. W. (1993). Similar hydrophobic replacements of Leu 99 and Phe 153 within the core of T4 lysozyme have different structural and thermodynamic consequences, J. Mol. Biol. 229, 747–769.CrossRefGoogle Scholar
Escher, M. C. (1961). ‘Graphic work of M. C. Escher’. Oldbourne Book Co. Ltd. 2 Partman Street, London W1. Picture #12 – ‘Liberation’.Google Scholar
Fauchére, J.-L. & Pliska, V. (1983). Hydrophobic parameters π of amino acid side-chains form the partitioning of N-acetyl-amino-acid amides. Eur. J. Med. Chem.-Chim. Ther. 18, 369–375.Google Scholar
Finney, J. L. & Savage, H. F. J. (1988). Impenetrability revisited: New light on hydrogen bonding from neutron studies on biomolecule crystal hydrates. J. Mol. Structure 177, 23–41.CrossRefGoogle Scholar
Franks, F. (1972). Water a Comprehensive Treatise. Plenum Press, New York 1972 and later 7 volumes.Google Scholar
Garvey, E. P. & Matthews, C. R. (1989). Effects of multiple replacements at a single position on the folding and stability of dihydrofolate reductase from Escherichia coli 28, 2083–2093.Google Scholar
Gregoret, L. M. & Cohen, F. E. (1991). Protein folding: Effect of packing density on chain conformation. J. Mol. Biol. 219, 109–122.CrossRefGoogle ScholarPubMed
Hampsey, M. D., Das, G. & Sherman, F. (1988). Yeast iso-1-cytochrome c: genetic analysis of structural requirements. FEBS Lett. 231, 275–283.CrossRefGoogle ScholarPubMed
Handel, T. M., Williams, S. A. & Degrado, W. F. (1993). Metal ion-dependent modulation of the dynamics of a designed protein. Science, N. Y. 261, 879–885.CrossRefGoogle ScholarPubMed
Harbury, P. B., Zhang, T., Kim, P. S. & Alber, T. (1993). A switch between two-, three- and four-stranded coiled coils revealed by mutants of the GCN4 leucine zipper. Science, N. Y. 262, 1401–1407.CrossRefGoogle ScholarPubMed
Hellinga, H. W., Wynn, R. & Richards, F. M. (1992). The hydrophobic core of Escherichia coli thioredoxin shows a high tolerance to nonconservative single amino acid substitutions. Biochemistry 31, 11203–11209.CrossRefGoogle Scholar
Henn, A. R. & Kauzmann, W. (1989). Equation of state of a random network, continuum model of liquid water. J. Phys. Chem. 93, 3770–3783.CrossRefGoogle Scholar
Herzberg, O. & Moult, J. (1991). Analysis of the steric strain in the polypeptide backbone of protein molecules. Proteins Struc. Func. Gen. 11, 223–229.CrossRefGoogle ScholarPubMed
Hurley, J. H., Baase, W. A. & Matthews, B. W. (1992). Design and structural analysis of alternative hydrophobic core packing arrangements in bacteriophage T4 lysozyme. J. Mol. Biol. 224, 1143–1159.CrossRefGoogle ScholarPubMed
Janin, J., Wodak, S., Levitt, M. & Maigret, B. (1978). Conformation of amino acid side-chains in proteins. J. Mol. Biol. 125, 357–386.CrossRefGoogle ScholarPubMed
Jordan, S. R. & Pabo, C. O. (1988). Structure of the lambda complex at 2·5 Å resolution: details of the repressor–operator interactions. Science, N. Y. 242, 893–899.CrossRefGoogle ScholarPubMed
Jorgensen, W. L., Chandrasekhar, J. & Madura, J. D. (1983). Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935.CrossRefGoogle Scholar
Jorgensen, W. L., Madura, J. D. & Swenson, C. J. (1984). Optimized intermolecular potential functions for liquid hydrocarbons. J. Am. Chem. Soc. 106, 6638–6646.CrossRefGoogle Scholar
Jorgensen, W. L. (1986). Optimized intermolecular potential functions for liquid alcohols. Journal of Physical Chemistry 90, 1276–1284.CrossRefGoogle Scholar
Jorgensen, W. L. & Severance, D. L. (1990). Aromatic-aromatic interactions: Free energy profiles for the benzene dimer in water, chloroform, and liquid benzene. J. Am. Chem. Soc. 112, 4768–4774.CrossRefGoogle Scholar
Kamtekar, S., Schiffer, J. M., Xiong, H., Babik, J. M. & Hecht, M. H. (1993). Protein design by binary patterning of polar and nonpolar amino acids. Science, N. Y. 262, 1680–1685.CrossRefGoogle ScholarPubMed
Karpusas, M., Baase, W. A., Matsumura, M. & Matthews, B. W. (1989). Hydrophobic packing in T4 lysozyme probed by cavity-filling mutants. Proc. Natl. Acad. Sci. U.S.A. 86, 8237–8241.CrossRefGoogle ScholarPubMed
Kauzmann, W. (1987). Thermodynamics of unfolding. Nature 325, 763–764.CrossRefGoogle Scholar
Kellis, J. T., Nyberg, K. & Fersht, A. R. (1989). Energetics of complementary side-chain packing in a protein hydrophobic core. Biochemistry 28, 4914–4922.CrossRefGoogle Scholar
Kim, E. E., Varadarajan, R., Wyckoff, H. W. & Richards, F. M. (1992). Refinement of the crystal structure of ribonuclease S. Comparison with and between the various ribonuclease A structures. Biochemistry 31, 12304–12314.CrossRefGoogle ScholarPubMed
Kitaigordosky, A. I. (1961). Organic Chemical Crystallography Consultants Bureau, New York (authorized English translation 1961, original Russian text published 1955).Google Scholar
Kitaigordosky, A. I. (1973). Molecular Crystals and Molecules. Academic Press, New York.Google Scholar
Kleina, L. G. & Miller, J. H. (1990). Genetic studies of the lac repressor XIII. Extensive amino acid replacements generated by the use of natural and synthetic nonsense suppressors. J. Mol. Biol. 212, 295–318.CrossRefGoogle ScholarPubMed
Kuntz, I. D. & Crippen, G. M. (1979). Protein densities. Int. J. Peptide Protein Res. 13, 223–228.CrossRefGoogle ScholarPubMed
Langsetmo, K., Fuchs, J. A. & Woodward, C. (1991). The conserved, buried aspartic acid in oxidized Escherichia coli thioredoxin has a ps of 7·5. Its titration produces a related shift in global stability. Biochemistry 30, 7603–7609.CrossRefGoogle Scholar
Langsetmo, K., Fuchs, J. A., Woodward, C. & Sharp, K. A. (1991). Linkage of thioredoxin stability to titration of ionizable groups with perturbed pKa. Biochemistry 30, 7609–7614.CrossRefGoogle ScholarPubMed
Lee, B. (1985). The physical origin of the low solubility of nonpolar solutes in water. Biopolymers 24, 813–823.CrossRefGoogle ScholarPubMed
Lee, B. (1991). Solvent reorganization contribution to the transfer thermodynamics of small nonpolar molecules. Biopolymers 31, 993–1008.CrossRefGoogle Scholar
Lee, B. (1993). Estimation of the maximum change in stability of globular proteins upon mutation of a hydrophobic residue to another of smaller size. Protein Science 2, 733–738.CrossRefGoogle ScholarPubMed
Lee, C. & Levitt, M. (1991). Accurate prediction of the stability and activity effects of site-directed mutagenesis on a protein core. Nature, Lond. 352, 448–451.CrossRefGoogle ScholarPubMed
Lee, C. & Subbiah, S. (1991). Prediction of protein side-chain conformation by packing optimization. J. Mol. Biol. 217, 373–388.CrossRefGoogle ScholarPubMed
Lesk, A. M. & Chothia, C. (1980). How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. J. Mol. Biol. 136, 223–268.CrossRefGoogle ScholarPubMed
Lim, W. A. & Sauer, R. T. (1989). Alternative packing arrangements in the hydrophobic core of lambda repressor. Nature, Lond. 339, 31–36.CrossRefGoogle ScholarPubMed
Lim, W. A. & Sauer, R. T. (1991). The role in internal packing interactions in determining the structure and stability of a protein. J. Mol. Biol. 219, 359–376.CrossRefGoogle ScholarPubMed
Lim, W. A., Farruggio, D. C. & Sauer, R. T. (1992). Structural and energetic consequences of disruptive mutations in a protein core. Biochemistry 31, 4324–4333.CrossRefGoogle Scholar
Lim, W. A., Hodel, A., Sauer, R. T. & Richards, F. M. (1993). Structure of a λ repressor mutant with improved hydrophobic core packing. Proc. Natl. Acad. Sci. U.S.A. (in press).Google Scholar
Lovejoy, B., Choe, S., Cascio, D., McRorie, D. K., Degrado, W. F. & Eisenberg, D. (1993). Crystal structure of a synthetic triple-stranded α-helical bundle. Science, N. Y. 259, 1288–1293.CrossRefGoogle ScholarPubMed
Malcolm, B. A., Wilson, K. P., Matthews, B. W., Kirsch, J. F. & Wilson, A. C. (1990). Ancestral lysozymes reconstructed, neutrality tested, and thermostability linked to hydrocarbon packing. Nature, Lond. 344, 86–89.CrossRefGoogle Scholar
Markiewicz, P., Kleina, L., Cruz, C., Ehret, S. & Miller, J. H. (1993). Analysis of 4,000 altered Escherichia coli lac repressors resulting from suppression of nonsense mutations at 328 positions in the lacI gene. J. Mol. Biol. (In the press).Google Scholar
McGregor, M. J., Islam, S. A. & Sternberg, M. J. E. (1987). Analysis of the relationship between side-chain conformation and secondary structure in globular proteins. J. Mol. Biol. 198, 295–310.CrossRefGoogle ScholarPubMed
McRee, D. E., Redford, S. M., Getzoff, E. D., Lepock, J. R., Hallewell, R. A. & Tainer, J. A. (1990). Changes in crystallographic structure and thermostability of a Cu, Zn superoxide dismutase mutant resulting from the removal of a buried cysteine. J. Biol. Chem. 265, 14234–14241.CrossRefGoogle ScholarPubMed
Morris, A. L., MacArthur, M. W., Hutchinson, E. G. & Thornton, J. M. (1992). Stereochemical quality of protein structure coordinates. Proteins Struc. Func. Gen. 12, 345–364.CrossRefGoogle ScholarPubMed
Narten, A. H. (1977). X-ray diffraction pattern and models of liquid benzene, J. Chem. Phys. 67, 2102–2108.CrossRefGoogle Scholar
O'Shea, E. K., Klemm, J. D., Kim, P. K. & Alber, T. (1991). X-ray structure of the GN4 leucine zipper, a two-stranded, parallel coiled coil. Science, N. Y. 254, 539–544.CrossRefGoogle Scholar
Pace, C. N. (1992). Contribution of the hydrophobic effect to globular protein stability. J. Mol. Biol. 226, 29–35.CrossRefGoogle ScholarPubMed
Parsell, D. A. & Sauer, R. T. (1989). The structural stability of a protein is an important determinant of its proteolytic susceptibility in Escherichia coli. J. Biol. Chem. 264, 7590–7595.CrossRefGoogle ScholarPubMed
Perutz, M. F., Kendrew, J. C. & Watson, H. C. (1965). Structure and function of haemoglobin II. Some relations between polypeptide chain configuration and amino acid sequence. J. Mol. Biol. 13, 669–678.CrossRefGoogle Scholar
Ponder, J. W. & Richards, F. M. (1987). Tertiary templates for proteins: Use of packing criteria in the enumeration of allowed sequences for different structural classes. J. Mol. Biol. 193, 775–791.CrossRefGoogle ScholarPubMed
Privalov, P. L. & Gill, S. J. (1988). Stability of protein structure and hydrophobic interaction. Adv. Protein Chem. 39, 191–234.CrossRefGoogle ScholarPubMed
Rashin, A. A. & Honig, B. (1984). On the environment of ionizable groups in globular proteins. J. Mol. Biol. 173, 515–521.CrossRefGoogle Scholar
Rashin, A. A., Iofin, M. & Honig, B. (1986). Internal cavities and buried waters in globular proteins. Biochemistry 25, 3619–3625.CrossRefGoogle ScholarPubMed
Reidhaar-Olson, J. F. & Sauer, R. T. (1988). Combinatorial cassette mutagenesis as a probe of the informational content of protein sequences. Science, N. Y. 241, 53–57.CrossRefGoogle ScholarPubMed
Reidhaar-Olson, J. F. & Sauer, R. T. (1990). Functionally acceptable substitutions in two α-helical regions of λ repressor. Proteins Struc. Func. Gen. 7, 306–316.CrossRefGoogle ScholarPubMed
Rennell, D., Bouvier, S. E., Hardy, L. W. & Poteete, A. R. (1991). Systematic mutation of bacteriophage T4 lysozyme. J. Mol. Biol. 222, 67–87.CrossRefGoogle ScholarPubMed
Richards, F. M. (1977). Areas, volumes, packing, and protein structure. Ann. Rev. Biophys. Bioeng. 6, 151–176.CrossRefGoogle ScholarPubMed
Richards, F. M. & Richmond, T. J. (1978). Solvents, interfaces and protein structure. Ciba Symposium, ‘Molecular Interactions and Activity in Proteins’, No. 60, 23–45.CrossRefGoogle Scholar
Richards, F. M. (1986). Protein design: Are we ready? Protein Structure, Folding and Design, 171–196.Google Scholar
Richards, F. M. & Kundrot, C. E. (1988). Identification of structural motifs from protein coordinate data: Secondary structure and first-level supersecondary structure. Proteins 3, 71–84.CrossRefGoogle ScholarPubMed
Richards, F. M. (1992). Folded and Unfolded Proteins: An Introduction. In Protein Folding (ed. Creighton, T. E.), New York: W. H. Freeman & Co. Chapter 1, pp. 1–58.Google Scholar
Rose, G. D. & Wolfenden, R. (1993). Hydrogen bonding, hydrophobicity, packing and folding. Ann. Rev. Biophys. & Struct. Biol. 22, 381–415.CrossRefGoogle Scholar
Sandberg, W. S. & Terwilliger, T. C. (1989). Influence of interior packing and hydrophobicity on the stability of a protein. Science, N. Y. 245, 54–57.CrossRefGoogle ScholarPubMed
Sandberg, W. S. & Terwilliger, T. C. (1991 a). Energetics of repacking a protein interior. Proc. Natl. Acad. Sci. U.S.A. 88, 1–5.CrossRefGoogle ScholarPubMed
Sandberg, W. S. & Terwilliger, T. C. (1991 b). Repacking protein interiors. Tibtech. 9, 59–63.CrossRefGoogle ScholarPubMed
Schoenborn, B. P. (1969). Structure of alkaline metmyoglobin-xenon complex. J. Mol. Biol. 45, 297–303.CrossRefGoogle ScholarPubMed
Serrano, L., Bycroft, M. & Fersht, A. R. (1991). Aromatic-aromatic interactions and protein stability investigation by double-mutant cycles. J. Mol. Biol. 218, 465–475.CrossRefGoogle ScholarPubMed
Sharp, K. A., Nicholls, A., Friedman, R. & Honig, B. (1991). Extracting hydrophobic free energies from experimental data: Relationship to protein folding and theoretical models. Biochemistry 30, 9686–9697.CrossRefGoogle ScholarPubMed
Shortle, D., Stites, W. E. & Meeker, A. K. (1990). Contributions of the large hydrophobic amino acids to the stability of staphylococcal nuclease. Biochemistry 29, 8033–8041.CrossRefGoogle Scholar
Shortle, D. (1992). Mutational studies of protein structures and their stabilities. Q. Rev. Biophys. 25, 205–250.CrossRefGoogle ScholarPubMed
Shortle, D., Chan, H. S. & Dill, K. A. (1992). Modeling the effects of mutations on the denatured states of proteins. Protein Science 1, 201–215.CrossRefGoogle ScholarPubMed
Simonson, T. & Brunger, A. T. (1992). Thermodynamics of protein-peptide interactions in the ribonuclease-S system studies by molecular dynamics and free energy calculations. Biochemistry 31, 8661–8674.CrossRefGoogle ScholarPubMed
Soper, A. K. & Phillips, M. G. (1986). A new determination of the structure of water at 25 °C. Chem. Phys. 107, 47–60.CrossRefGoogle Scholar
Stites, W. E., Gittis, A. G., Lattman, E. E. & Shortle, D. (1991). In a staphylococcal nuclease mutant the side-chain of a lysine replacing valine 66 is fully buried in the hydrophobic core. J. Mol. Biol. 221, 7–14.Google Scholar
Thornton, J. M. (1992). Protein Structures: The End Point of the Folding Pathway. In Protein Folding (ed. Creighton, T. E.), W. H. Freeman Co., New York, Chapter 2, pp. 59–81.Google Scholar
Tilton, R. F., Kuntz, I. D. & Petsko, G. A. (1984). Cavities in proteins: Structure of a metmyoglobin-xenon complex solved to 1·9 Å. Biochemistry 23, 2849–2857.CrossRefGoogle ScholarPubMed
Tilton, R. F., Singh, U. C., Kuntz, I. D. & Kollman, P. A. (1988). Protein-ligand dynamics A96 picosecond simulation of a myoglobin-xenon complex. J. Mol. Biol. 199 195–211.CrossRefGoogle Scholar
Tsuji, T., Chrunyk, B. A., Chen, X. & Matthews, C. R. (1993). Mutagenic analysis of the interior packing of an α/β barrel protein. Effects on the stabilities and rates of interconversion of the native and partially folded forms of the α subunit of tryptophan synthase. Biochemistry 32, 5566–5575.CrossRefGoogle ScholarPubMed
Varadarajan, R. & Richards, F. M. (1992). Crystallographic structures of ribonuclease S variants with nonpolar substitution at position 13: Packing and cavities. Biochemistry 31, 12315–12327.CrossRefGoogle ScholarPubMed
Wynn, R. & Richards, F. M. (1993). Unnatural amino acid packing mutants of Escherichia coli thioredoxin produced by combined mutagenesis/chemical modification techniques. Protein Science 2, 395–403.CrossRefGoogle ScholarPubMed