A novel web server predicts amino acid residue protection against hydrogen-deuterium exchange

MOTIVATION To clarify the relationship between structural elements and polypeptide chain mobility, a set of statistical analyses of structures is necessary. Because at present proteins with determined spatial structures are much less numerous than those with amino acid sequence known, it is important to be able to predict the extent of proton protection from hydrogen-deuterium (HD) exchange basing solely on the protein primary structure. RESULTS Here we present a novel web server aimed to predict the degree of amino acid residue protection against HD exchange solely from the primary structure of the protein chain under study. On the basis of the amino acid sequence, the presented server offers the following three possibilities (predictors) for user's choice. First, prediction of the number of contacts occurring in this protein, which is shown to be helpful in estimating the number of protons protected against HD exchange (sensitivity 0.71). Second, probability of H-bonding in this protein, which is useful for finding the number of unprotected protons (specificity 0.71). The last is the use of an artificial predictor. Also, we report on mass spectrometry analysis of HD exchange that has been first applied to free amino acids. Its results showed a good agreement with theoretical data (number of protons) for 10 globular proteins (correlation coefficient 0.73). We pioneered in compiling two datasets of experimental HD exchange data for 35 proteins. AVAILABILITY The H-Protection server is available for users at http://bioinfo.protres.ru/ogp/ SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

[1]  Peter G Wolynes,et al.  Prediction of native-state hydrogen exchange from perfectly funneled energy landscapes. , 2011, Journal of the American Chemical Society.

[2]  Christopher M. Dobson,et al.  Structural basis of the stability of a lysozyme molten globule , 1995, Nature Structural Biology.

[3]  A M Gronenborn,et al.  Kinetics of folding of the all-beta sheet protein interleukin-1 beta. , 1993, Science.

[4]  G. Rose,et al.  Turns in peptides and proteins. , 1985, Advances in protein chemistry.

[5]  S. Casares,et al.  The native state conformational ensemble of the SH3 domain from alpha-spectrin. , 1999, Biochemistry.

[6]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[7]  M. Y. Lobanov,et al.  Comparison of experimental and theoretical data on hydrogen-deuterium exchange for ten globular proteins , 2012, Biochemistry (Moscow).

[8]  Michail Yu. Lobanov,et al.  FoldAmyloid: a method of prediction of amyloidogenic regions from protein sequence , 2010, Bioinform..

[9]  Michele Vendruscolo,et al.  Prediction of local structural stabilities of proteins from their amino acid sequences. , 2007, Structure.

[10]  S Walter Englander,et al.  Protein hydrogen exchange: Testing current models , 2012, Protein science : a publication of the Protein Society.

[11]  J. Markley,et al.  Hydrogen exchange in unligated and ligated staphylococcal nuclease. , 1993, Biochemistry.

[12]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[13]  S. Morin,et al.  NMR dynamics of PSE-4 beta-lactamase: an interplay of ps-ns order and mus-ms motions in the active site. , 2009, Biophysical journal.

[14]  On the use of hydrogen/deuterium exchange mass spectrometry data to improve de novo protein structure prediction. , 2009, Rapid communications in mass spectrometry : RCM.

[15]  C. Woodward,et al.  Hydrogen exchange identifies native-state motional domains important in protein folding. , 1993, Biochemistry.

[16]  Tracy M. Handel,et al.  Detection of rare partially folded molecules in equilibrium with the native conformation of RNaseH , 1996, Nature Structural Biology.

[17]  T. Holak,et al.  Comparison of the amide proton exchange behavior of the rapidly formed folding intermediate and the native state of an antibody scFv fragment , 1997, FEBS letters.

[18]  L. Franzoni,et al.  New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers[S] , 2010, Journal of Lipid Research.

[19]  K. Takahashi,et al.  Studies on thermolysin. I. Inactivation of thermolysin by rose bengal-catalyzed photooxidation--evidence for the presence of a critical histidine residue. , 1971, Journal of biochemistry.

[20]  P. Alexander,et al.  Assessment of stability differences in the protein G B1 and B2 domains from hydrogen-deuterium exchange: comparison with calorimetric data. , 1995, Biochemistry.

[21]  Geerten W Vuister,et al.  A closed binding pocket and global destabilization modify the binding properties of an alternatively spliced form of the second PDZ domain of PTP-BL. , 2004, Structure.

[22]  C Redfield,et al.  Comparison of the structural and dynamical properties of holo and apo bovine alpha-lactalbumin by NMR spectroscopy. , 2001, Journal of molecular biology.

[23]  Solution structure of the C‐terminal domain of multiprotein bridging factor 1 (MBF1) of Trichoderma reesei , 2009, Proteins.

[24]  A. Fontana.  Structure and stability of thermophilic enzymes. Studies on thermolysin. , 1988, Biophysical chemistry.

[25]  L Serrano,et al.  Amide hydrogen exchange and internal dynamics in the chemotactic protein CheY from Escherichia coli. , 1997, Journal of molecular biology.

[26]  S. Englander.  Hydrogen exchange and mass spectrometry: A historical perspective , 2006, Journal of the American Society for Mass Spectrometry.

[27]  C Cambillau,et al.  Thermal unfolding of a llama antibody fragment: a two-state reversible process. , 2001, Biochemistry.

[28]  A. D. Robertson,et al.  Temperature and pH dependences of hydrogen exchange and global stability for ovomucoid third domain. , 1996, Biochemistry.

[29]  M. Y. Lobanov,et al.  Prediction of amino acid residues protected from hydrogen-deuterium exchange in a protein chain , 2009, Biochemistry (Moscow).

[30]  K Wüthrich,et al.  Amide proton exchange in the alpha-amylase polypeptide inhibitor Tendamistat studied by two-dimensional 1H nuclear magnetic resonance. , 1987, Biochemistry.

[31]  H. Dyson,et al.  Absence of a stable intermediate on the folding pathway of protein A , 1997, Protein science : a publication of the Protein Society.

[32]  V. Dötsch,et al.  Solution structure of the Escherichia coli YojN histidine-phosphotransferase domain and its interaction with cognate phosphoryl receiver domains. , 2004, Journal of molecular biology.

[33]  A. Fersht,et al.  Hydrogen exchange in chymotrypsin inhibitor 2 probed by denaturants and temperature. , 1997, Journal of molecular biology.

[34]  L Mayne,et al.  Determinants of protein hydrogen exchange studied in equine cytochrome c , 1998, Protein science : a publication of the Protein Society.

[35]  D. Moras,et al.  Correlation between segmental mobility and the location of antigenic determinants in proteins , 1984, Nature.

[36]  F. Cutruzzolà,et al.  Backbone dynamics and hydrogen exchange of Pseudomonas aeruginosa ferricytochrome c551 , 2002, JBIC Journal of Biological Inorganic Chemistry.

[37]  D. Jacobs,et al.  Protein flexibility predictions using graph theory , 2001, Proteins.

[38]  C. Pace,et al.  Conformational stability of ribonuclease T1 determined by hydrogen‐deuterium exchange , 1997, Protein science : a publication of the Protein Society.

[39]  M. S. Briggs,et al.  Hydrogen exchange in native and alcohol forms of ubiquitin. , 1992, Biochemistry.

[40]  J. Markley,et al.  Solution structure and backbone dynamics of component IV Glycera dibranchiata monomeric hemoglobin-CO. , 1998, Biochemistry.

[41]  F. Damberger,et al.  Solution structure and activation mechanism of ubiquitin-like small archaeal modifier proteins. , 2011, Journal of molecular biology.

[42]  J. Feeney,et al.  NMR Structures of Apo L. casei Dihydrofolate Reductase and Its Complexes with Trimethoprim and NADPH: Contributions to Positive Cooperative Binding from Ligand-Induced Refolding, Conformational Changes, and Interligand Hydrophobic Interactions , 2011, Biochemistry.

[43]  D T Jones,et al.  Protein secondary structure prediction based on position-specific scoring matrices. , 1999, Journal of molecular biology.

[44]  Michail Yu. Lobanov,et al.  FoldUnfold: web server for the prediction of disordered regions in protein chain , 2006, Bioinform..

[45]  A. Fersht,et al.  Detection and characterization of a folding intermediate in barnase by NMR , 1990, Nature.

[46]  C. Yu,et al.  Comparison of the structural stability of two homologous toxins isolated from the Taiwan cobra (Naja naja atra) venom. , 2000, Biochemistry.

[47]  Frank Kjeldsen,et al.  Backbone carbonyl group basicities are related to gas-phase fragmentation of peptides and protein folding. , 2007, Angewandte Chemie.

[48]  Oxana V Galzitskaya,et al.  Prediction of Residue Status to Be Protected or Not Protected From Hy-drogen Exchange Using Amino Acid Sequence Only , 2008, The Open Biochemistry Journal.

[49]  Qian Yi,et al.  Direct evidence for a two‐state protein unfolding transition from hydrogen‐deuterium exchange, mass spectrometry, and NMR , 1996, Protein science : a publication of the Protein Society.