Quantitative use of chemical shifts for the modeling of protein complexes

Despite recent advances in the modeling of protein‐protein complexes by docking, additional information is often required to identify the best solutions. For this purpose, NMR data deliver valuable restraints that can be used in the sampling and/or the scoring stage, like in the data‐driven docking approach HADDOCK that can make use of NMR chemical shift perturbation (CSP) data to define the binding site on each protein and drive the docking. We show here that a quantitative use of chemical shifts (CS) in the scoring stage can help to resolve ambiguities. A quantitative CS‐RMSD score based on 1Hα,13Cα, and 15N chemical shifts ranks the best solutions always at the top, as demonstrated on a small benchmark of four complexes. It is implemented in a new docking protocol, CS‐HADDOCK, which combines CSP data as ambiguous interaction restraints in the sampling stage with the CS‐RMSD score in the final scoring stage. This combination of qualitative and quantitative use of chemical shifts increases the reliability of data‐driven docking for the structure determination of complexes from limited NMR data. Proteins 2011; © 2011 Wiley‐Liss, Inc.

[1]  Holger Gohlke,et al.  Steering Protein-Ligand Docking with Quantitative NMR Chemical Shift Perturbations , 2009, J. Chem. Inf. Model..

[2]  Michele Vendruscolo,et al.  Protein structure determination from NMR chemical shifts , 2007, Proceedings of the National Academy of Sciences.

[3]  David S. Wishart,et al.  CS23D: a web server for rapid protein structure generation using NMR chemical shifts and sequence data , 2008, Nucleic Acids Res..

[4]  Jaime L. Stark,et al.  Rapid protein-ligand costructures using chemical shift perturbations. , 2008, Journal of the American Chemical Society.

[5]  C. Dominguez,et al.  HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. , 2003, Journal of the American Chemical Society.

[6]  D. Wyss,et al.  Structures of protein-protein complexes are docked using only NMR restraints from residual dipolar coupling and chemical shift perturbations. , 2002, Journal of the American Chemical Society.

[7]  M. Williamson,et al.  C alpha and C beta carbon-13 chemical shifts in proteins from an empirical database. , 1999, Journal of biomolecular NMR.

[8]  Simon W. Ginzinger,et al.  CheckShift improved: fast chemical shift reference correction with high accuracy , 2009, Journal of biomolecular NMR.

[9]  Mitsuo Iwadate,et al.  Cα and Cβ Carbon-13 Chemical Shifts in Proteins From an Empirical Database , 1999 .

[10]  A. Bonvin,et al.  The HADDOCK web server for data-driven biomolecular docking , 2010, Nature Protocols.

[11]  D. Wyss,et al.  Alignment of weakly interacting molecules to protein surfaces using simulations of chemical shift perturbations , 2000, Journal of biomolecular NMR.

[12]  D. Wishart,et al.  Rapid and accurate calculation of protein 1H, 13C and 15N chemical shifts , 2003, Journal of Biomolecular NMR.

[13]  D. Case,et al.  A new analysis of proton chemical shifts in proteins , 1991 .

[14]  Jakob Dogan,et al.  Thermodynamics of folding and binding in an affibody:affibody complex. , 2006, Journal of molecular biology.

[15]  Alexandre M J J Bonvin,et al.  HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets , 2007, Proteins.

[16]  A. Bax,et al.  Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology , 2007, Journal of biomolecular NMR.

[17]  Miron Livny,et al.  BioMagResBank , 2007, Nucleic Acids Res..

[18]  David S Wishart,et al.  A simple method to adjust inconsistently referenced 13C and 15N chemical shift assignments of proteins , 2005, Journal of biomolecular NMR.

[19]  E. Zuiderweg,et al.  Mapping protein-protein interactions in solution by NMR spectroscopy. , 2002, Biochemistry.

[20]  L. Waskell,et al.  Characterization and calculation of a cytochrome c-cytochrome b5 complex using NMR data. , 2005, Biochemistry.

[21]  Kai J. Kohlhoff,et al.  Fast and accurate predictions of protein NMR chemical shifts from interatomic distances. , 2009, Journal of the American Chemical Society.

[22]  Oliver F. Lange,et al.  Consistent blind protein structure generation from NMR chemical shift data , 2008, Proceedings of the National Academy of Sciences.

[23]  N. Tjandra,et al.  Structural Basis of Focal Adhesion Localization of LIM-only Adaptor PINCH by Integrin-linked Kinase* , 2009, Journal of Biological Chemistry.

[24]  M. McCoy,et al.  Spatial localization of ligand binding sites from electron current density surfaces calculated from NMR chemical shift perturbations. , 2002, Journal of the American Chemical Society.

[25]  Martin J Packer,et al.  Determination of protein-ligand binding modes using complexation-induced changes in (1)h NMR chemical shift. , 2008, Journal of medicinal chemistry.

[26]  Wolfram Gronwald,et al.  Combined chemical shift changes and amino acid specific chemical shift mapping of protein–protein interactions , 2007, Journal of biomolecular NMR.

[27]  C. Hunter,et al.  Use of quantitative 1H NMR chemical shift changes for ligand docking into barnase , 2009, Journal of biomolecular NMR.

[28]  Michele Vendruscolo,et al.  Structure determination of protein-protein complexes using NMR chemical shifts: case of an endonuclease colicin-immunity protein complex. , 2008, Journal of the American Chemical Society.

[29]  S. Wodak,et al.  Assessment of CAPRI predictions in rounds 3–5 shows progress in docking procedures , 2005, Proteins.

[30]  Marc F Lensink,et al.  Docking and scoring protein interactions: CAPRI 2009 , 2010, Proteins.

[31]  Alexandre M. J. J. Bonvin,et al.  SAMPLEX: Automatic mapping of perturbed and unperturbed regions of proteins and complexes , 2010, BMC Bioinformatics.

[32]  Zhiping Weng,et al.  Docking unbound proteins using shape complementarity, desolvation, and electrostatics , 2002, Proteins.

[33]  Maxim Totrov,et al.  Improving CAPRI predictions: Optimized desolvation for rigid‐body docking , 2005, Proteins.

[34]  K. Merz,et al.  Fast semiempirical calculations for nuclear magnetic resonance chemical shifts: a divide-and-conquer approach. , 2004, The Journal of chemical physics.

[35]  Reino Laatikainen,et al.  4D prediction of protein 1H chemical shifts , 2009, Journal of biomolecular NMR.

[36]  D. S. Garrett,et al.  Identification by NMR of the binding surface for the histidine-containing phosphocarrier protein HPr on the N-terminal domain of enzyme I of the Escherichia coli phosphotransferase system. , 1997, Biochemistry.

[37]  G. Moore,et al.  Protein-protein interactions in colicin E9 DNase-immunity protein complexes. 1. Diffusion-controlled association and femtomolar binding for the cognate complex. , 1995, Biochemistry.

[38]  J. Markley,et al.  Empirical correlation between protein backbone 15N and 13C secondary chemical shifts and its application to nitrogen chemical shift re-referencing , 2009, Journal of biomolecular NMR.

[39]  David S Wishart,et al.  RefDB: A database of uniformly referenced protein chemical shifts , 2003, Journal of biomolecular NMR.