Article

You have full text access to this OnlineOpen article

StoneHinge: Hinge prediction by network analysis of individual protein structures

  1. Kevin S. Keating1,
  2. Samuel C. Flores2,3,†,
  3. Mark B. Gerstein1,3,4,
  4. Leslie A. Kuhn5,6,7,*

Article first published online: 15 DEC 2008

DOI: 10.1002/pro.38

Issue

Protein Science

Protein Science

Volume 18, Issue 2, pages 359–371, February 2009

Additional Information

How to Cite

Keating, K. S., Flores, S. C., Gerstein, M. B. and Kuhn, L. A. (2009), StoneHinge: Hinge prediction by network analysis of individual protein structures. Protein Science, 18: 359–371. doi: 10.1002/pro.38

Author Information

  1. 1

    Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut

  2. 2

    Department of Physics, Yale University, New Haven, Connecticut

  3. 3

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut

  4. 4

    Department of Computer Science, Yale University, New Haven, Connecticut

  5. 5

    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan

  6. 6

    Department of Computer Science and Engineering, Michigan State University, East Lansing, Michigan

  7. 7

    Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan

  1. †

    James H. Clark Center S231, MC 5448, Stanford University, Stanford, California

*Protein Structural Analysis and Design Lab, 502C Biochemistry Building, Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319

Publication History

  1. Issue published online: 30 JAN 2009
  2. Article first published online: 15 DEC 2008
  3. Accepted manuscript online: 15 DEC 2008 12:00AM EST
  4. Manuscript Accepted: 17 NOV 2008
  5. Manuscript Revised: 12 NOV 2008
  6. Manuscript Received: 14 AUG 2008

Funded by

  • NIH. Grant Numbers: GM 72970, GM 67249, AI 53877, T15 LM07056
  • Keck Foundation: AL Williams Professorship Funds
  • Simbios
  • NIH Roadmap for Medical Research. Grant Number: U54 GM072970

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (723K)

References

  • 1
    Hayward S, Kitao A, Berendsen HJ ( 1997) Model-free methods of analyzing domain motions in proteins from simulation: a comparison of normal mode analysis and molecular dynamics simulation of lysozyme. Proteins 27: 425–437.
    Direct Link:
  • 2
    Scheibel T, Lindquist SL ( 2001) The role of conformational flexibility in prion propagation and maintenance for Sup35p. Nat Struct Biol 8: 958–962.
  • 3
    Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ ( 2005) Geometry-based flexible and symmetric protein docking. Proteins 60: 224–231.
    Direct Link:
  • 4
    Cozzini P, Kellogg GE, Spyrakis F, Abraham DJ, Costantino G, Emerson A, Fanelli F, Gohlke H, Kuhn LA, Morris GM, Orozco M, Pertinez TA, Rizzi M, Sotriffer CA ( 2008) Target flexibility: an emerging consideration in drug discovery and design. J Med Chem 51: 6237–6255.
  • 5
    Gerstein M, Lesk AM, Chothia C ( 1994) Structural mechanisms for domain movements in proteins. Biochemistry 33: 6739–6749.
  • 6
    Gerstein M, Jansen R, Johnson T, Tsai J, Krebs W, Studying macromolecular motions in a database framework: from structure to sequence. In: ThorpeM, DuxburyP, Eds. ( 1999) Rigidity theory and applications. New York, NY: Kluwer Academic/Plenum Publishers.
  • 7
    Krebs W, The database of macromolecular motions: a standardized system for analyzing and visualizing macromolecular motions in a database framework. Dissertation ( 2001) Molecular Biophysics and Biochemistry. New Haven: Yale University, p 288.
  • 8
    Maiorov V, Abagyan R ( 1997) A new method for modeling large-scale rearrangements of protein domains. Proteins 27: 410–424.
    Direct Link:
  • 9
    Zhang XJ, Wozniak JA, Matthews BW ( 1995) Protein flexibility and adaptability seen in 25 crystal forms of T4 lysozyme. J Mol Biol 250: 527–552.
  • 10
    Hayward S, Berendsen HJ ( 1998) Systematic analysis of domain motions in proteins from conformational change: new results on citrate synthase and T4 lysozyme. Proteins 30: 144–154.
    Direct Link:
  • 11
    Shatsky M, Nussinov R, Wolfson HJ ( 2002) Flexible protein alignment and hinge detection. Proteins 48: 242–256.
    Direct Link:
  • 12
    Kundu S, Sorensen DC, Phillips GN,Jr ( 2004) Automatic domain decomposition of proteins by a Gaussian network model. Proteins 57: 725–733.
    Direct Link:
  • 13
    Gerstein M, Schulz G, Chothia C ( 1993) Domain closure in adenylate kinase. Joints on either side of two helices close like neighboring fingers. J Mol Biol 229: 494–501.
  • 14
    Ahn S, Milner AJ, Futterer K, Konopka M, Ilias M, Young TW, White SA ( 2001) The “open” and “closed” structures of the type-C inorganic pyrophosphatases from Bacillus subtilis and Streptococcus gordonii. J Mol Biol 313: 797–811.
  • 15
    Bjorkman AJ, Mowbray SL ( 1998) Multiple open forms of ribose-binding protein trace the path of its conformational change. J Mol Biol 279: 651–664.
  • 16
    Zehfus MH ( 1994) Binary discontinuous compact protein domains. Protein Eng 7: 335–340.
  • 17
    Holm L, Sander C ( 1998) Dictionary of recurrent domains in protein structures. Proteins 33: 88–96.
    Direct Link:
  • 18
    Holm L, Sander C ( 1994) Parser for protein folding units. Proteins 19: 256–268.
    Direct Link:
  • 19
    Islam SA, Luo J, Sternberg MJ ( 1995) Identification and analysis of domains in proteins. Protein Eng 8: 513–525.
  • 20
    Siddiqui AS, Barton GJ ( 1995) Continuous and discontinuous domains: an algorithm for the automatic generation of reliable protein domain definitions. Protein Sci 4: 872–884.
    Direct Link:
  • 21
    Swindells MB ( 1995) A procedure for detecting structural domains in proteins. Protein Sci 4: 103–112.
    Direct Link:
  • 22
    Swindells MB ( 1995) A procedure for the automatic determination of hydrophobic cores in protein structures. Protein Sci 4: 93–102.
    Direct Link:
  • 23
    Painter J, Merritt EA ( 2006) Optimal description of a protein structure in terms of multiple groups undergoing TLS motion. Acta Crystallogr D62: 439–450.
  • 24
    Flores SC, Gerstein MB ( 2007) FlexOracle: predicting flexible hinges by identification of stable domains. BMC Bioinformatics 8: 215.
  • 25
    Flores SC, Lu LJ, Yang J, Carriero N, Gerstein MB ( 2007) Hinge Atlas: relating protein sequence to sites of structural flexibility. BMC Bioinformatics 8: 167.
  • 26
    Hinsen K ( 1998) Analysis of domain motions by approximate normal mode calculations. Proteins 33: 417–429.
    Direct Link:
  • 27
    Jacobs DJ, Rader AJ, Kuhn LA, Thorpe MF ( 2001) Protein flexibility predictions using graph theory. Proteins 44: 150–165.
    Direct Link:
  • 28
    Bahar I, Atilgan AR, Erman B ( 1997) Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential. Fold Des 2: 173–181.
  • 29
    Flores SC, Keating KS, Painter J, Morcos FG, Nguyen K, Merritt E, Kuhn LA, Gerstein M ( 2008) HingeMaster: normal mode hinge prediction approach and integration of complementary predictors. Proteins 73: 299–319.
    Direct Link:
  • 30
    Krebs WG, Gerstein M ( 2000) The morph server: a standardized system for analyzing and visualizing macromolecular motions in a database framework. Nucleic Acids Res 28: 1665–1675.
  • 31
    Flores S, Echols N, Milburn D, Hespenheide B, Keating K, Lu J, Wells S, Yu EZ, Thorpe M, Gerstein M ( 2006) The database of macromolecular motions: new features added at the decade mark. Nucleic Acids Res 34: D296–D301.
  • 32
    Shatsky M, Nussinov R, Wolfson HJ ( 2004) FlexProt: alignment of flexible protein structures without a predefinition of hinge regions. J Comput Biol 11: 83–106.
  • 33
    Tsigelny I, Greenberg JP, Cox S, Nichols WL, Taylor SS, Ten Eyck LF ( 1999) 600 ps molecular dynamics reveals stable substructures and flexible hinge points in cAMP dependent protein kinase. Biopolymers 50: 513–524.
    Direct Link:
  • 34
    Hsiao CD, Sun YJ, Rose J, Wang BC ( 1996) The crystal structure of glutamine-binding protein from Escherichia coli. J Mol Biol 262: 225–242.
  • 35
    Kumar A, Widen SG, Williams KR, Kedar P, Karpel RL, Wilson SH ( 1990) Studies of the domain structure of mammalian DNA polymerase beta. Identification of a discrete template binding domain. J Biol Chem 265: 2124–2131.
  • 36
    Ikura M, Clore GM, Gronenborn AM, Zhu G, Klee CB, Bax A ( 1992) Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256: 632–638.
  • 37
    Meador WE, Means AR, Quiocho FA ( 1992) Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex. Science 257: 1251–1255.
  • 38
    van der Spoel D, de Groot BL, Hayward S, Berendsen HJ, Vogel HJ ( 1996) Bending of the calmodulin central helix: a theoretical study. Protein Sci 5: 2044–2053.
    Direct Link:
  • 39
    DeLano WL ( 2002) The PyMOL molecular graphics system. San Carlos, CA: DeLano Scientific.
  • 40
    Raymer ML, Sanschagrin PC, Punch WF, Venkataraman S, Goodman ED, Kuhn LA ( 1997) Predicting conserved water-mediated and polar ligand interactions in proteins using a K-nearest-neighbors genetic algorithm. J Mol Biol 265: 445–464.
  • 41
    Mayer KL, Earley MR, Gupta S, Pichumani K, Regan L, Stone MJ ( 2003) Covariation of backbone motion throughout a small protein domain. Nat Struct Biol 10: 962–965.
  • 42
    Lei M, Zavodszky MI, Kuhn LA, Thorpe MF ( 2004) Sampling protein conformations and pathways. J Comput Chem 25: 1133–1148.
    Direct Link:
  • 43
    Zavodszky MI, Sanschagrin PC, Korde RS, Kuhn LA ( 2002) Distilling the essential features of a protein surface for improving protein-ligand docking, scoring, and virtual screening. J Comput Aided Mol Des 16: 883–902.
  • 44
    Zavodszky MI, Lei M, Thorpe MF, Day AR, Kuhn LA ( 2004) Modeling correlated main-chain motions in proteins for flexible molecular recognition. Proteins 57: 243–261.
    Direct Link:
  • 45
    Ahmed A, Gohlke H ( 2006) Multiscale modeling of macromolecular conformational changes combining concepts from rigidity and elastic network theory. Proteins 63: 1038–1051.
    Direct Link:
  • 46
    Chun HM, Padilla CE, Chin DN, Watanabe M, Karlov VI, Alper HE, Soosaar K, Blair KB, Becker OM, Caves LSD, Nagle R, Haney D, Farmer B ( 2000) MBO(N)D: a multibody method for long-time molecular dynamics simulations. J Comput Chem 21: 159–184.
    Direct Link:
  • 47
    Williams MA, Goodfellow JM, Thornton JM ( 1994) Buried waters and internal cavities in monomeric proteins. Protein Sci 3: 1224–1235.
    Direct Link:
  • 48
    Gohlke H, Kuhn LA, Case DA ( 2004) Change in protein flexibility upon complex formation: analysis of Ras-Raf using molecular dynamics and a molecular framework approach. Proteins 56: 322–337.
    Direct Link:
  • 49
    Lindahl E, Hess B, van der Spoel D ( 2001) GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7: 306–317.
  • 50
    Hespenheide BM, Rader AJ, Thorpe MF, Kuhn LA ( 2002) Identifying protein folding cores from the evolution of flexible regions during unfolding. J Mol Graph Model 21: 195–207.
  • 51
    Rader AJ, Hespenheide BM, Kuhn LA, Thorpe MF ( 2002) Protein unfolding: rigidity lost. Proc Natl Acad Sci USA 99: 3540–3545.
  • 52
    Tanford C ( 1980) The hydrophobic effect: formation of micelles and biological membranes, 2nd Edn. New York: Wiley.
  • 53
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE ( 2000) The protein data bank. Nucleic Acids Res 28: 235–242.
  • 54
    Karlsson R, Zheng J, Xuong N, Taylor SS, Sowadski JM ( 1993) Structure of the mammalian catalytic subunit of cAMP-dependent protein kinase and an inhibitor peptide displays an open conformation. Acta Crystallogr D Biol Crystallogr 49: 381–388.
    Direct Link:
  • 55
    Zheng J, Trafny EA, Knighton DR, Xuong NH, Taylor SS, Ten Eyck LF, Sowadski JM ( 1993) 2.2 A refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide inhibitor. Acta Crystallogr D Biol Crystallogr 49: 362–365.
    Direct Link:
  • 56
    Huang DB, Ainsworth CF, Stevens FJ, Schiffer M ( 1996) Three quaternary structures for a single protein. Proc Natl Acad Sci USA 93: 7017–7021.
  • 57
    Oh BH, Pandit J, Kang CH, Nikaido K, Gokcen S, Ames GF, Kim SH ( 1993) Three-dimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand. J Biol Chem 268: 11348–11355.
  • 58
    Diederichs K, Schulz GE ( 1991) The refined structure of the complex between adenylate kinase from beef heart mitochondrial matrix and its substrate AMP at 1.85 A resolution. J Mol Biol 217: 541–549.
  • 59
    Muller CW, Schulz GE ( 1992) Structure of the complex between adenylate kinase from Escherichia coli and the inhibitor Ap5A refined at 1.9 A resolution. A model for a catalytic transition state. J Mol Biol 224: 159–177.
  • 60
    Sun YJ, Rose J, Wang BC, Hsiao CD ( 1998) The structure of glutamine-binding protein complexed with glutamine at 1.94 A resolution: comparisons with other amino acid binding proteins. J Mol Biol 278: 219–229.
  • 61
    Pelletier H, Sawaya MR, Kumar A, Wilson SH, Kraut J ( 1994) Structures of ternary complexes of rat DNA polymerase beta, a DNA template-primer, and ddCTP. Science 264: 1891–1903.
  • 62
    Sawaya MR, Pelletier H, Kumar A, Wilson SH, Kraut J ( 1994) Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism. Science 264: 1930–1935.
  • 63
    Kuboniwa H, Tjandra N, Grzesiek S, Ren H, Klee CB, Bax A ( 1995) Solution structure of calcium-free calmodulin. Nat Struct Biol 2: 768–776.
  • 64
    Chattopadhyaya R, Meador WE, Means AR, Quiocho FA ( 1992) Calmodulin structure refined at 1.7 A resolution. J Mol Biol 228: 1177–1192.
  • 65
    Bjorkman AJ, Binnie RA, Zhang H, Cole LB, Hermodson MA, Mowbray SL ( 1994) Probing protein-protein interactions. The ribose-binding protein in bacterial transport and chemotaxis. J Biol Chem 269: 30206–30211.
  • 66
    Gallagher T, Alexander P, Bryan P, Gilliland GL ( 1994) Two crystal structures of the B1 immunoglobulin-binding domain of streptococcal protein G and comparison with NMR. Biochemistry 33: 4721–4729.
  • 67
    Xiao B, Shi G, Chen X, Yan H, Ji X ( 1999) Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents. Structure 7: 489–496.
  • 68
    Kallen J, Mikol V, Taylor P, Walkinshaw MD ( 1998) X-ray structures and analysis of 11 cyclosporin derivatives complexed with cyclophilin A. J Mol Biol 283: 435–449.
  • 69
    Suguna K, Bott RR, Padlan EA, Subramanian E, Sheriff S, Cohen GH, Davies DR ( 1987) Structure and refinement at 1.8 A resolution of the aspartic proteinase from Rhizopus chinensis. J Mol Biol 196: 877–900.
  • 70
    Suguna K, Padlan EA, Smith CW, Carlson WD, Davies DR ( 1987) Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action. Proc Natl Acad Sci USA 84: 7009–7013.
  • 71
    Gibbs MR, Moody PC, Leslie AG ( 1990) Crystal structure of the aspartic acid-199 –> asparagine mutant of chloramphenicol acetyltransferase to 2.35-A resolution: structural consequences of disruption of a buried salt bridge. Biochemistry 29: 11261–11265.
  • 72
    Leslie AG ( 1990) Refined crystal structure of type III chloramphenicol acetyltransferase at 1.75 A resolution. J Mol Biol 213: 167–186.
  • 73
    Moult J, Sussman F, James MN ( 1985) Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 A resolution. J Mol Biol 182: 555–566.
  • 74
    James MN, Sielecki AR, Brayer GD, Delbaere LT, Bauer CA ( 1980) Structures of product and inhibitor complexes of Streptomyces griseus protease A at 1.8 A resolution. A model for serine protease catalysis. J Mol Biol 144: 43–88.
View Full Article with Supporting Information (HTML) Get PDF (723K)