Skip to main content
NCBI home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1996 Jul;5(7):1406–1420. doi: 10.1002/pro.5560050719

Experimentally observed conformation-dependent geometry and hidden strain in proteins.

P A Karplus 1
PMCID: PMC2143451  PMID: 8819173

Abstract

A database has been compiled documenting the peptide conformations and geometries from 70 diverse proteins refined at 1.75 A or better. Analysis of the well-ordered residues within the database shows phi, psi-distributions that have more fine structure than is generally observed. Also, clear evidence is presented that the peptide covalent geometry depends on conformation, with the interpeptide N-C alpha-C bond angle varying by nearly +/-5 degrees from its standard value. The observed deviations from standard peptide geometry are greatest near the edges of well-populated regions, consistent with strain occurring in these conformations. Minimization of such hidden strain could be an important factor in thermostability of proteins. These empirical data describing how equilibrium peptide geometry varies as a function of conformation confirm and extend quantum mechanics calculations, and have predictive value that will aid both theoretical and experimental analyses of protein structure.

Full Text

The Full Text of this article is available as a PDF (5.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adzhubei A. A., Sternberg M. J. Left-handed polyproline II helices commonly occur in globular proteins. J Mol Biol. 1993 Jan 20;229(2):472–493. doi: 10.1006/jmbi.1993.1047. [DOI] [PubMed] [Google Scholar]
  2. Anderson A. G., Hermans J. Microfolding: conformational probability map for the alanine dipeptide in water from molecular dynamics simulations. Proteins. 1988;3(4):262–265. doi: 10.1002/prot.340030408. [DOI] [PubMed] [Google Scholar]
  3. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  4. Blaber M., Zhang X. J., Lindstrom J. D., Pepiot S. D., Baase W. A., Matthews B. W. Determination of alpha-helix propensity within the context of a folded protein. Sites 44 and 131 in bacteriophage T4 lysozyme. J Mol Biol. 1994 Jan 14;235(2):600–624. doi: 10.1006/jmbi.1994.1016. [DOI] [PubMed] [Google Scholar]
  5. Bradley E. A., Stewart D. E., Adams M. W., Wampler J. E. Investigations of the thermostability of rubredoxin models using molecular dynamics simulations. Protein Sci. 1993 Apr;2(4):650–665. doi: 10.1002/pro.5560020415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chakrabartty A., Baldwin R. L. Stability of alpha-helices. Adv Protein Chem. 1995;46:141–176. [PubMed] [Google Scholar]
  7. Chan M. K., Mukund S., Kletzin A., Adams M. W., Rees D. C. Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase. Science. 1995 Mar 10;267(5203):1463–1469. doi: 10.1126/science.7878465. [DOI] [PubMed] [Google Scholar]
  8. Creamer T. P., Rose G. D. Alpha-helix-forming propensities in peptides and proteins. Proteins. 1994 Jun;19(2):85–97. doi: 10.1002/prot.340190202. [DOI] [PubMed] [Google Scholar]
  9. Dauter Z., Lamzin V. S., Wilson K. S. Proteins at atomic resolution. Curr Opin Struct Biol. 1995 Dec;5(6):784–790. doi: 10.1016/0959-440x(95)80011-5. [DOI] [PubMed] [Google Scholar]
  10. Dunbrack R. L., Jr, Karplus M. Backbone-dependent rotamer library for proteins. Application to side-chain prediction. J Mol Biol. 1993 Mar 20;230(2):543–574. doi: 10.1006/jmbi.1993.1170. [DOI] [PubMed] [Google Scholar]
  11. Efimov A. V. Standard structures in proteins. Prog Biophys Mol Biol. 1993;60(3):201–239. doi: 10.1016/0079-6107(93)90015-c. [DOI] [PubMed] [Google Scholar]
  12. Fields B. A., Bartsch H. H., Bartunik H. D., Cordes F., Guss J. M., Freeman H. C. Accuracy and precision in protein crystal structure analysis: two independent refinements of the structure of poplar plastocyanin at 173 K. Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):709–730. doi: 10.1107/S0907444994003021. [DOI] [PubMed] [Google Scholar]
  13. Görbitz C. H., Etter M. C. Hydrogen bond connectivity patterns and hydrophobic interactions in crystal structures of small, acyclic peptides. Int J Pept Protein Res. 1992 Feb;39(2):93–110. doi: 10.1111/j.1399-3011.1992.tb00778.x. [DOI] [PubMed] [Google Scholar]
  14. Hermans J., Anderson A. G., Yun R. H. Differential helix propensity of small apolar side chains studied by molecular dynamics simulations. Biochemistry. 1992 Jun 23;31(24):5646–5653. doi: 10.1021/bi00139a031. [DOI] [PubMed] [Google Scholar]
  15. Herzberg O., Moult J. Analysis of the steric strain in the polypeptide backbone of protein molecules. Proteins. 1991;11(3):223–229. doi: 10.1002/prot.340110307. [DOI] [PubMed] [Google Scholar]
  16. Hobohm U., Sander C. Enlarged representative set of protein structures. Protein Sci. 1994 Mar;3(3):522–524. doi: 10.1002/pro.5560030317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hobohm U., Scharf M., Schneider R., Sander C. Selection of representative protein data sets. Protein Sci. 1992 Mar;1(3):409–417. doi: 10.1002/pro.5560010313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  19. Karplus P. A., Schulz G. E. Refined structure of glutathione reductase at 1.54 A resolution. J Mol Biol. 1987 Jun 5;195(3):701–729. doi: 10.1016/0022-2836(87)90191-4. [DOI] [PubMed] [Google Scholar]
  20. Kuriyan J., Karplus M., Petsko G. A. Estimation of uncertainties in X-ray refinement results by use of perturbed structures. Proteins. 1987;2(1):1–12. doi: 10.1002/prot.340020102. [DOI] [PubMed] [Google Scholar]
  21. Lazaridis T., Archontis G., Karplus M. Enthalpic contribution to protein stability: insights from atom-based calculations and statistical mechanics. Adv Protein Chem. 1995;47:231–306. doi: 10.1016/s0065-3233(08)60547-1. [DOI] [PubMed] [Google Scholar]
  22. MacArthur M. W., Thornton J. M. Influence of proline residues on protein conformation. J Mol Biol. 1991 Mar 20;218(2):397–412. doi: 10.1016/0022-2836(91)90721-h. [DOI] [PubMed] [Google Scholar]
  23. Milner-White E. J. Situations of gamma-turns in proteins. Their relation to alpha-helices, beta-sheets and ligand binding sites. J Mol Biol. 1990 Nov 20;216(2):386–397. [PubMed] [Google Scholar]
  24. Morris A. L., MacArthur M. W., Hutchinson E. G., Thornton J. M. Stereochemical quality of protein structure coordinates. Proteins. 1992 Apr;12(4):345–364. doi: 10.1002/prot.340120407. [DOI] [PubMed] [Google Scholar]
  25. Nilges M., Clore G. M., Gronenborn A. M. Determination of three-dimensional structures of proteins from interproton distance data by dynamical simulated annealing from a random array of atoms. Circumventing problems associated with folding. FEBS Lett. 1988 Oct 24;239(1):129–136. doi: 10.1016/0014-5793(88)80559-3. [DOI] [PubMed] [Google Scholar]
  26. Ramachandran G. N., Sasisekharan V. Conformation of polypeptides and proteins. Adv Protein Chem. 1968;23:283–438. doi: 10.1016/s0065-3233(08)60402-7. [DOI] [PubMed] [Google Scholar]
  27. Rice L. M., Brünger A. T. Torsion angle dynamics: reduced variable conformational sampling enhances crystallographic structure refinement. Proteins. 1994 Aug;19(4):277–290. doi: 10.1002/prot.340190403. [DOI] [PubMed] [Google Scholar]
  28. Rooman M. J., Kocher J. P., Wodak S. J. Extracting information on folding from the amino acid sequence: accurate predictions for protein regions with preferred conformation in the absence of tertiary interactions. Biochemistry. 1992 Oct 27;31(42):10226–10238. doi: 10.1021/bi00157a009. [DOI] [PubMed] [Google Scholar]
  29. Roterman I. K., Lambert M. H., Gibson K. D., Scheraga H. A. A comparison of the CHARMM, AMBER and ECEPP potentials for peptides. II. Phi-psi maps for N-acetyl alanine N'-methyl amide: comparisons, contrasts and simple experimental tests. J Biomol Struct Dyn. 1989 Dec;7(3):421–453. doi: 10.1080/07391102.1989.10508503. [DOI] [PubMed] [Google Scholar]
  30. Russell R. J., Hough D. W., Danson M. J., Taylor G. L. The crystal structure of citrate synthase from the thermophilic archaeon, Thermoplasma acidophilum. Structure. 1994 Dec 15;2(12):1157–1167. doi: 10.1016/s0969-2126(94)00118-9. [DOI] [PubMed] [Google Scholar]
  31. Schimmel P. R., Flory P. J. Conformational energies and configurational statistics of copolypeptides containing L-proline. J Mol Biol. 1968 May 28;34(1):105–120. doi: 10.1016/0022-2836(68)90237-4. [DOI] [PubMed] [Google Scholar]
  32. Scully J., Hermans J. Backbone flexibility and stability of reverse turn conformation in a model system. J Mol Biol. 1994 Jan 14;235(2):682–694. doi: 10.1006/jmbi.1994.1020. [DOI] [PubMed] [Google Scholar]
  33. Srinivasan R., Rose G. D. LINUS: a hierarchic procedure to predict the fold of a protein. Proteins. 1995 Jun;22(2):81–99. doi: 10.1002/prot.340220202. [DOI] [PubMed] [Google Scholar]
  34. Stites W. E., Meeker A. K., Shortle D. Evidence for strained interactions between side-chains and the polypeptide backbone. J Mol Biol. 1994 Jan 7;235(1):27–32. doi: 10.1016/s0022-2836(05)80008-7. [DOI] [PubMed] [Google Scholar]
  35. Stites W. E., Pranata J. Empirical evaluation of the influence of side chains on the conformational entropy of the polypeptide backbone. Proteins. 1995 Jun;22(2):132–140. doi: 10.1002/prot.340220206. [DOI] [PubMed] [Google Scholar]
  36. Swindells M. B., MacArthur M. W., Thornton J. M. Intrinsic phi, psi propensities of amino acids, derived from the coil regions of known structures. Nat Struct Biol. 1995 Jul;2(7):596–603. doi: 10.1038/nsb0795-596. [DOI] [PubMed] [Google Scholar]
  37. Thornton J. M., Jones D. T., MacArthur M. W., Orengo C. M., Swindells M. B. Protein folds: towards understanding folding from inspection of native structures. Philos Trans R Soc Lond B Biol Sci. 1995 Apr 29;348(1323):71–79. doi: 10.1098/rstb.1995.0047. [DOI] [PubMed] [Google Scholar]
  38. Wilmot C. M., Thornton J. M. Beta-turns and their distortions: a proposed new nomenclature. Protein Eng. 1990 May;3(6):479–493. doi: 10.1093/protein/3.6.479. [DOI] [PubMed] [Google Scholar]
  39. Winkler F. K., Dunitz J. D. The non-planar amide group. J Mol Biol. 1971 Jul 14;59(1):169–182. doi: 10.1016/0022-2836(71)90419-0. [DOI] [PubMed] [Google Scholar]
  40. Zimmerman S. S., Pottle M. S., Némethy G., Scheraga H. A. Conformational analysis of the 20 naturally occurring amino acid residues using ECEPP. Macromolecules. 1977 Jan-Feb;10(1):1–9. doi: 10.1021/ma60055a001. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES