Protein structure prediction using sparse dipolar coupling data.

Residual dipolar coupling (RDC) represents one of the most exciting emerging NMR techniques for protein structure studies. However, solving a protein structure using RDC data alone is still a highly challenging problem. We report here a computer program, RDC-PROSPECT, for protein structure prediction based on a structural homolog or analog of the target protein in the Protein Data Bank (PDB), which best aligns with the (15)N-(1)H RDC data of the protein recorded in a single ordering medium. Since RDC-PROSPECT uses only RDC data and predicted secondary structure information, its performance is virtually independent of sequence similarity between a target protein and its structural homolog/analog, making it applicable to protein targets beyond the scope of current protein threading techniques. We have tested RDC-PROSPECT on all (15)N-(1)H RDC data (representing 43 proteins) deposited in the BioMagResBank (BMRB) database. The program correctly identified structural folds for 83.7% of the target proteins, and achieved an average alignment accuracy of 98.1% residues within a four-residue shift.

[1]  S. V. Van Doren,et al.  Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual dipolar couplings. , 2003, Biochemistry.

[2]  H. Atreya,et al.  A tracked approach for automated NMR assignments in proteins (TATAPRO) , 2000, Journal of biomolecular NMR.

[3]  A M Gronenborn,et al.  A robust method for determining the magnitude of the fully asymmetric alignment tensor of oriented macromolecules in the absence of structural information. , 1998, Journal of magnetic resonance.

[4]  S. Henikoff,et al.  Amino acid substitution matrices from protein blocks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Santos,et al.  Structural basis for the network of functional cooperativities in cytochrome c(3) from Desulfovibrio gigas: solution structures of the oxidised and reduced states. , 2000, Journal of molecular biology.

[6]  Bruce Randall Donald,et al.  3D structural homology detection via unassigned residual dipolar couplings , 2003, Computational Systems Bioinformatics. CSB2003. Proceedings of the 2003 IEEE Bioinformatics Conference. CSB2003.

[7]  S. B. Needleman,et al.  A general method applicable to the search for similarities in the amino acid sequence of two proteins. , 1970, Journal of molecular biology.

[8]  Tao Jiang,et al.  Automated assignment of backbone NMR peaks using constrained bipartite matching , 2002, Comput. Sci. Eng..

[9]  J H Prestegard,et al.  NMR structures of biomolecules using field oriented media and residual dipolar couplings , 2000, Quarterly Reviews of Biophysics.

[10]  J. Prestegard,et al.  New techniques in structural NMR — anisotropic interactions , 1998, Nature Structural Biology.

[11]  Guangshun Wang,et al.  Solution Structure of the Phosphoryl Transfer Complex between the Cytoplasmic A Domain of the Mannitol Transporter IIMannitol and HPr of the Escherichia coliPhosphotransferase System* , 2002, The Journal of Biological Chemistry.

[12]  R. Levy,et al.  Protein structural motif recognition via NMR residual dipolar couplings. , 2001, Journal of the American Chemical Society.

[13]  Nico Tjandra,et al.  NMR dipolar couplings for the structure determination of biopolymers in solution , 2002 .

[14]  C. Dobson,et al.  A refined solution structure of hen lysozyme determined using residual dipolar coupling data , 2001, Protein science : a publication of the Protein Society.

[15]  A. Bax,et al.  Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium. , 1997, Science.

[16]  J. Feeney,et al.  NMR-based solution structure of the complex of Lactobacillus casei dihydrofolate reductase with trimethoprim and NADPH. , 2002, Journal of biomolecular NMR.

[17]  J Weigelt,et al.  NMR structure of the N-terminal domain of E. coli DnaB helicase: implications for structure rearrangements in the helicase hexamer. , 1999, Structure.

[18]  Eva Thulin,et al.  Recognition of protein folds via dipolar couplings , 1999 .

[19]  D. Wishart,et al.  The 13C Chemical-Shift Index: A simple method for the identification of protein secondary structure using 13C chemical-shift data , 1994, Journal of biomolecular NMR.

[20]  J. Hus,et al.  Determination of protein backbone structure using only residual dipolar couplings. , 2001, Journal of the American Chemical Society.

[21]  G. Marius Clore,et al.  Improving the Packing and Accuracy of NMR Structures with a Pseudopotential for the Radius of Gyration , 1999 .

[22]  A. Bax.  Weak alignment offers new NMR opportunities to study protein structure and dynamics , 2003, Protein science : a publication of the Protein Society.

[23]  Yuichi Harano,et al.  Complete protein structure determination using backbone residual dipolar couplings and sidechain rotamer prediction , 2004, Journal of Structural and Functional Genomics.

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

[25]  Brian E Coggins,et al.  PACES: Protein sequential assignment by computer-assisted exhaustive search , 2003, Journal of biomolecular NMR.

[26]  A. Gronenborn,et al.  The solution structure of a fungal AREA protein-DNA complex: an alternative binding mode for the basic carboxyl tail of GATA factors. , 1998, Journal of molecular biology.

[27]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[28]  Jens Meiler,et al.  DipoCoup: A versatile program for 3D-structure homology comparison based on residual dipolar couplings and pseudocontact shifts , 2000, Journal of biomolecular NMR.

[29]  A M Gronenborn,et al.  The solution structure of the Leu22-->Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity. , 1998, Journal of molecular biology.

[30]  Ad Bax,et al.  Solution structure of Ca2+–calmodulin reveals flexible hand-like properties of its domains , 2001, Nature Structural Biology.

[31]  Eric W. Weisstein,et al.  The CRC concise encyclopedia of mathematics , 1999 .

[32]  J H Prestegard,et al.  Rapid determination of protein folds using residual dipolar couplings. , 2000, Journal of molecular biology.

[33]  B D Sykes,et al.  Chemical shifts as a tool for structure determination. , 1994, Methods in enzymology.

[34]  J. Richardson,et al.  Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. , 1999, Journal of molecular biology.

[35]  Ad Bax,et al.  Prediction of Sterically Induced Alignment in a Dilute Liquid Crystalline Phase: Aid to Protein Structure Determination by NMR , 2000 .

[36]  N. Tjandra,et al.  Solution structure of human GAIP (Galpha interacting protein): a regulator of G protein signaling. , 1999, Journal of molecular biology.

[37]  A. Bax,et al.  Dipolar couplings in macromolecular structure determination. , 2001, Methods in enzymology.

[38]  H N Moseley,et al.  Automatic determination of protein backbone resonance assignments from triple resonance nuclear magnetic resonance data. , 2001, Methods in enzymology.

[39]  Sachdev S Sidhu,et al.  Origins of PDZ Domain Ligand Specificity , 2003, The Journal of Biological Chemistry.

[40]  Dong Xu,et al.  PROSPECT II: protein structure prediction program for genome-scale applications. , 2003, Protein engineering.

[41]  Burkhard Rost,et al.  DSSPcont: continuous secondary structure assignments for proteins , 2003, Nucleic Acids Res..

[42]  J. Swarbrick,et al.  The three-dimensional structure of the Nudix enzyme diadenosine tetraphosphate hydrolase from Lupinus angustifolius L. , 2000, Journal of molecular biology.

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

[44]  R A Sayle,et al.  RASMOL: biomolecular graphics for all. , 1995, Trends in biochemical sciences.

[45]  A. Gronenborn,et al.  Solution structure of cyanovirin-N, a potent HIV-inactivating protein , 1998, Nature Structural Biology.

[46]  F. Richards,et al.  The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. , 1992, Biochemistry.

[47]  J. Hus,et al.  De novo determination of protein structure by NMR using orientational and long-range order restraints. , 2000, Journal of molecular biology.

[48]  A. Annila,et al.  NMR solution structure of calerythrin, an EF-hand calcium-binding protein from Saccharopolyspora erythraea. , 2003, European journal of biochemistry.

[49]  D. S. Garrett,et al.  Solution structure of the 40,000 Mr phosphoryl transfer complex between the N-terminal domain of enzyme I and HPr , 1999, Nature Structural Biology.

[50]  Harold A. Scheraga,et al.  Exact solutions for chemical bond orientations from residual dipolar couplings , 2002, Journal of biomolecular NMR.

[51]  Geoff Kelly,et al.  NMR structure of the DNA-binding domain of the cell cycle protein Mbp1 from Saccharomyces cerevisiae. , 2003, Biochemistry.

[52]  B. Rost,et al.  Prediction of protein secondary structure at better than 70% accuracy. , 1993, Journal of molecular biology.

[53]  A. Bax,et al.  Solution structure of DinI provides insight into its mode of RecA inactivation , 2000, Protein science : a publication of the Protein Society.

[54]  Y. Pommier,et al.  Solution Structure of Anti-HIV-1 and Anti-Tumor Protein MAP30 Structural Insights into Its Multiple Functions , 1999, Cell.

[55]  F. Richards,et al.  Relationship between nuclear magnetic resonance chemical shift and protein secondary structure. , 1991, Journal of molecular biology.

[56]  J. Hus,et al.  A novel interactive tool for rigid-body modeling of multi-domain macromolecules using residual dipolar couplings , 2001, Journal of biomolecular NMR.

[57]  D. Baker,et al.  De novo determination of protein backbone structure from residual dipolar couplings using Rosetta. , 2002, Journal of the American Chemical Society.

[58]  H. Anton,et al.  Elementary linear algebra with applications , 1987 .

[59]  Daniel W. A. Buchan,et al.  A structural perspective on genome evolution. , 2003 .

[60]  J H Prestegard,et al.  A dipolar coupling based strategy for simultaneous resonance assignment and structure determination of protein backbones. , 2001, Journal of the American Chemical Society.

[61]  K. Brew,et al.  NMR structure of tissue inhibitor of metalloproteinases-1 implicates localized induced fit in recognition of matrix metalloproteinases. , 2000, Journal of molecular biology.

[62]  P E Bourne,et al.  Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. , 1998, Protein engineering.

[63]  J H Prestegard,et al.  Structural and dynamic analysis of residual dipolar coupling data for proteins. , 2001, Journal of the American Chemical Society.

[64]  S. Grzesiek,et al.  Structural basis for antibiotic recognition by the TipA class of multidrug‐resistance transcriptional regulators , 2003, The EMBO journal.

[65]  A Elofsson,et al.  Assessing the performance of fold recognition methods by means of a comprehensive benchmark. , 1996, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[66]  A. Sali,et al.  Protein Structure Prediction and Structural Genomics , 2001, Science.

[67]  A. Hinck,et al.  Solution structure and backbone dynamics of the TGFbeta type II receptor extracellular domain. , 2003, Biochemistry.

[68]  Gaetano T Montelione,et al.  Automated protein fold determination using a minimal NMR constraint strategy , 2003, Protein science : a publication of the Protein Society.

[69]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[70]  D. Draper,et al.  Refining the overall structure and subdomain orientation of ribosomal protein S4 delta41 with dipolar couplings measured by NMR in uniaxial liquid crystalline phases. , 1999, Journal of molecular biology.

[71]  I. Bertini,et al.  Paramagnetism-based versus classical constraints: An analysis of the solution structure of Ca Ln calbindin D9k , 2001, Journal of biomolecular NMR.

[72]  David J Weber,et al.  The use of dipolar couplings for determining the solution structure of rat apo‐S100B(ββ) , 2008, Protein science : a publication of the Protein Society.

[73]  P. Freemont,et al.  Solution structure and interaction surface of the C-terminal domain from p47: a major p97-cofactor involved in SNARE disassembly. , 2001, Journal of molecular biology.

[74]  J. Skolnick,et al.  Use of residual dipolar couplings as restraints in ab initio protein structure prediction , 2003, Biopolymers.

[75]  Conformations of the regulatory domain of cardiac troponin C examined by residual dipolar couplings , 2000 .

[76]  Letter to the Editor: 1H, 13C and 15N resonance assignments of domain 1 of receptor associated protein , 2003, Journal of biomolecular NMR.

[77]  H N Moseley,et al.  Automated analysis of NMR assignments and structures for proteins. , 1999, Current opinion in structural biology.

[78]  Homayoun Valafar,et al.  Rapid classification of a protein fold family using a statistical analysis of dipolar couplings , 2003, Bioinform..

[79]  J H Prestegard,et al.  Order matrix analysis of residual dipolar couplings using singular value decomposition. , 1999, Journal of magnetic resonance.

[80]  A M Gronenborn,et al.  Direct structure refinement against residual dipolar couplings in the presence of rhombicity of unknown magnitude. , 1998, Journal of magnetic resonance.

[81]  Y Xu,et al.  Protein threading using PROSPECT: Design and evaluation , 2000, Proteins.

[82]  Joel R Tolman,et al.  De novo determination of bond orientations and order parameters from residual dipolar couplings with high accuracy. , 2003, Journal of the American Chemical Society.

[83]  Ad Bax,et al.  Validation of Protein Structure from Anisotropic Carbonyl Chemical Shifts in a Dilute Liquid Crystalline Phase , 1998 .

[84]  Anthony K. Yan,et al.  A Polynomial-Time Nuclear Vector Replacement Algorithm for Automated NMR Resonance Assignments , 2004, J. Comput. Biol..

[85]  J R Tolman,et al.  Dipolar couplings as a probe of molecular dynamics and structure in solution. , 2001, Current opinion in structural biology.

[86]  Ad Bax,et al.  Evaluation of backbone proton positions and dynamics in a small protein by liquid crystal NMR spectroscopy. , 2003, Journal of the American Chemical Society.

[87]  A. Gronenborn,et al.  Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration , 1998, Nature Structural Biology.

[88]  J H Prestegard,et al.  Nuclear magnetic dipole interactions in field-oriented proteins: information for structure determination in solution. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[89]  J. R. Tolman.  A novel approach to the retrieval of structural and dynamic information from residual dipolar couplings using several oriented media in biomolecular NMR spectroscopy. , 2002, Journal of the American Chemical Society.

[90]  Ad Bax,et al.  Protein Structure Determination Using Molecular Fragment Replacement and NMR Dipolar Couplings , 2000 .

[91]  N. Tjandra,et al.  High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor. , 1999, Journal of molecular biology.

[92]  R. Levy,et al.  The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding. , 2003, Structure.

[93]  Kurt Wüthrich,et al.  Sequence-specific NMR assignment of proteins by global fragment mapping with the program Mapper , 2000, Journal of biomolecular NMR.

[94]  R. Levy,et al.  Protein backbone structure determination using only residual dipolar couplings from one ordering medium , 2001, Journal of biomolecular NMR.

[95]  Frédéric Barras,et al.  Direct structure determination using residual dipolar couplings: reaction-site conformation of methionine sulfoxide reductase in solution. , 2002, Journal of the American Chemical Society.

[96]  N. Alexandrov,et al.  SARFing the PDB. , 1996, Protein engineering.

[97]  G. Marius Clore,et al.  Use of dipolar 1H–15N and 1H–13C couplings in the structure determination of magnetically oriented macromolecules in solution , 1997, Nature Structural Biology.