Mapping Protein-Ligand Interaction by NMR Techniques: A Review

Abstract

Abstract:

Protein-ligand interaction studies play an important role in understanding of biological science, drug screening and drug design, thus have both scientific and economic meanings. In this review, NMR techniques that are being widely employed to study protein-ligand interaction are summarized. The important parameters used to characterize the intermolecular interaction are introduced firstly, followed by descriptions of the approaches for identifying interaction regions and how to extract valuable information related to intermolecular interaction. Finally, the NMR techniques that have been applied to map protein-ligand interaction are introduced with application examples.

Key words: NMR, protein, ligand, intermolecular interaction, drug screening

CLC Number:

O482.53

LIN Dong-Hai, HONG Jing. Mapping Protein-Ligand Interaction by NMR Techniques: A Review[J]. Chinese Journal of Magnetic Resonance, 2005, 22(3): 321-341.

References

[1] Craik D J，Wilce J A. Studies of protein-ligand interactions by NMR. In “rotein NMR Techniques”(Ed.: Reid D G) [M]. New Jersey: Humana Press Inc，1997. 195-232.

[2] Lian L Y ，Barsukov I L，Sutcliffe M J，et al. Protein-ligand interactions: exchange processes and determination of ligand conformation and protein-ligand contacts[J]. Method Enzymol，1994，239: 657-699.

[3] Lian L Y，Robert G C K. Effects of chemical exchange on NMR spectra，In "NMR of Macromolecules: A Practical Approach" (Ed.: Robert G C K) [M]. Oxford: Oxford University Press，1993. 153-182.

[4] Feeney J，Birdsall B. NMR studies of protein-ligand interactions. In "NMR of Macromolecules: A Practical Approach." (Ed.: Robert G C K) [M]. Oxford: Oxford University Press，1993. 183-216.

[5] Zuiderweg E R P. Mapping protein-protein interactions in solution by NMR spectroscopy[J]. Biochemistry，2002，41: 1-7.

[6] Liao Xin-|li(廖新丽)，Lin Dong-|hai(林东海). Protein Dynamics Studied by Heteronuclear Multi-dimensional NMR(用异核多维NMR技术研究蛋白质动力学)[J]. Chinese J Magn Reson(波谱学杂志)，2004，21(4): 385-396.

[7] Otting G，Wüthrich K. Heteronuclear filters in two-dimensional[1H，1H]-NMR spectroscopy: combined use with isotope labeling for studies of macromolecular conformation and intermolecular interactions[J]. Q Rev Biophys，1990，23: 39-96.

[8] Breeze A L. Isotope-filtered NMR methods for the study of biomolecular structure and interactions[J]. Prog NMR Spectrosc，2000，36: 323-372.

[9] Güntert P，Mumenthaler C，Wüthrich K. Torsion angle dynamics for NMR structure calculation with new program DYANA[J]. J Mol Biol，1997，273: 283-298.

[10] Brunger A T，Adams P D，Clore G M，et al. Crystallography & NMR system: A new software suite for macromolecular structure determination[J]. Acta Cryst, 1998，D54: 905-921.[11] Braunger A T. X-PLOR，Version 3.1 A system for X-ray Crystallography and NMR[M]. New Haven: Yale University Press，1993.

[12] Spitzfaden C，Braun W，Wider G，et al. Determination of the NMR solution structure of the cyclophilin A-cyclosporin A complex[J]. J Biomol NMR，1994，4: 463-482.

[13] Güntert P，Braun W，Wüthrich K. Efficient computation of three-dimensional protein structures in solution from nuclear magnetic resonance data using the program DIANA and the supporting programs CALIBA，HABAS and GLOMSA[J]. J Mol Biol，1991，217: 517-530.

[14] de Alba E，Tjandra N. NMR dipolar couplings for the structure determination of biopolymers in solution[J]. Prog NMR Spectrosc，2002， 40: 175-197.

[15] Fesik S W，Neri P，Meadows R，et al. A model of the cyclophilin/cyclosporin A (CSA) complex from NMR and X-ray data suggests that CSA binds as a transition-state analog[J]. J Am Chem Soc，1992，114: 3 165-3 166.

[16] Bennion C，Connolly S，Gensmantel N P，et al. Design and synthesis of some substrate analogue inhibitors of phospholipase A2 and investigations by NMR and molecular modeling into the binding interactions in the enzyme-inhibitor complex[J]. J Med Chem，1992，35: 2 939-2 951.

[17] Lippins G，Hallenga K, Van Belle D，et al. Transfer nuclear Overhauser effect study of the conformation of oxytocin bound to bovine neurophysin[J]. Biochemistry，1993，32: 9 423-9 434.

[18] Marcel J，Blommers J，Simon R. NMR of Weakly Binding Ligands. In “BioNMR in Drug Research” (Ed.: Zerbe O) [M]. New York: Wiley VCH，2003. 355-371.

[19] Wang Y-S，Liu D，Wyss D F. Competition STD NMR for the detection of high-affinity ligands and NMR-based screening[J]. Magn Reson Chem，2004，42: 485-489.

[20] Meyer B，Peters T. NMR Spectroscopy Techniques for Screening and Identifying Ligand Binding to Protein Receptors[J]. Angew Chem Int Edit，2003，42: 864-890.

[21] Hideo T，Tamiji N，Keiichiro K，et al. A novel NMR method for determining the interfaces of large protein-protein complexes[J]. Nat Struct Biol，2000，7 : 220-223.

[22] Dalvit C，Fogliattob G P，Stewartb A，et al. WaterLOGSY as a method for primary NMR screening: Practical aspects and range of applicability[J]. J Biomol NMR，2001，21: 349-359.

[23] Dalvit C，Pevarello P，Tato M，et al. Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water [J]. J Biomol NMR，2000，18: 65-68.

[24] Derrick T S，McCord E F，Larive C K. Analysis of Protein/Ligand interactions with NMR diffusion measurements: the importance of eliminating the protein background[J]. J Mag Reson, 2002，155: 217-225.

[25] Liu M，Nicholson J K，Lindon J C. Analysis of drug-protein binding using nuclear magnetic resonance based molecular diffusion measurements[J]. Anal Comm，1997，34: 225-228.

[26] Hajduk P J，Olejniczak E T，Fesik S W，et al. One-Dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules[J]. J Am Chem Soc，1997，119: 12 257-12 261.

[27] Dingley A J，Mackay J P，Shaw G L，et al. Measuring macromolecular diffusion using heteronuclear multiple-quantum pulsed-fieldgradient NMR[J]. J Biomol NMR，1997，10: 1-8.

[28] Tillett M L，Horsfield M A，Lian L Y，et al. Protein-ligand interaction measured by 15N-filtered diffusion experiments[J]. J Biomol NMR， 1999，13: 223-232.

[29] Moore J M. NMR techniques for characterization of ligand binding: utility for lead generation and optimization in drug discovery[J]. Biopolymers, 1999，51: 221-243.

[30] Jahnke W，Perez L B，Paris C G，et al. Second-site NMR screening with a spin-labeled first ligands[J]. J Am Chem Soc，2000，122: 7 394-7 395.

[31] Pellecchia M，Montgomery D L，Stevens S Y，et al. Structural insights into substrate binding by the molecular chaperone DnaK[J]. Nat Struct Biol，2000，7: 298-303.

[32] Stockman B，Dalvit C. NMR screening techniques in drug discovery and drug design[J]. Prog NMR Spectrosc，2002，41: 187-231.

[33] Hajduk P J，Meadows R P，Fesik S W. Discovering high-affinity ligands for proteins[J]. Science，1997，278: 497-499.

[34] Hajduk P J，Dinges J，Miknis G F，et al. NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein[J]. J Med Chem，1997，40: 3 144-3 150. 

[35] van Nuland N A，Kroon G J，Dijkstra K，et al. The NMR determination of the IIA (mtl) binding site on HPr of the Escherichia coli phosphoenol pyruvate- dependent phosphotransferase system[J]. Febs Lett，1993，315: 11-15.

[36] Dempsey C E. Hydrogen exchange in peptides and proteins using NMR spectroscopy[J]. Prog NMR Spectrosc，2001，39: 135-170.

[37] Miller S，Janin J，Lesk A M，et al. Interior and surface of monomeric proteins[J]. J Mol Biol，1987，196: 641-656.

[38] Bai Y，Milne J S，Mayne L，et al. Primary structure effects on peptide group hydrogen exchange[J]. Protein Struct Func Gen，1993，17: 75-86.

[39] Pellecchia M，Meininger D，Shen A L，et al. SEA-TROSY (Solvent Exposed Amides with TROSY): a method to resolve the problem of spectral overlap in very large proteins[J]. J Am Chem Soc，2001，123: 4 633-4 634.

[40] Lin D. Clean SEA-TROSY Experiments to map solvent exposed amides in large proteins[J]. Chin J Chem，2004，22: 1395-1398.

[41] Lin D，Sze K H，Cui Y F，et al. Clean SEA-HSQC: a method to map solvent amides in large non-deuterated proteins with gradientenhanced HSQC[J]. J Biomol NMR，2002，23: 317-322.

[42] Pellecchia M，Sem D，Wüthrich K. NMR in drug discovery[J]. Nat Rev Drug Discov，2002，11: 211-219.

[43] Shuker S B，Hajduk P J，Meadows R P，et al. Discovery high-affinity ligands for proteins: SAR-by-NMR[J]. Science，1996，274: 1 531-1 534.

[44] Coles M，Heller M，Kessler H. NMR-based screening technologies[J]. Drug Discov Today，2003，8: 803-810.

[45] Stockman B J，Dalvit C. NMR screening techniques in drug discovery and drug design[J]. Prog NMR Spectrosc，2002，41: 187-231.

[46] Stockman B J. NMR spectroscopy as a tool for structure-based drug design[J]. Prog NMR Spectrosc，1998，33: 109-151.

[47] Moore J M. NMR screening in drug discovery[J]. Curr Opin Biotech，1999，10: 54-58.

[48] Roberts G C K. NMR spectroscopy in structure-based drug design[J]. Curr Opin Biotech，1999，10: 42-47.

[49] Lepre C A. Strategies for NMR screening and library design. In “BioNMR in Drug Research” (Ed.: Zerbe O)[M]. New York: Wiley VCH， 2003. 391-415.

[50] Klaus W，Senn H. Strategies for hit finding using NMR. In “BioNMR in Drug Research” (Ed.: Zerbe O)[M]. New York: Wiley VCH，2003. 417-437.

[51] Blommers M J J，Florsheimer A，Jahnke W. Strategies for drug discovery using NMR. In “BioNMR in Drug Research”(Ed.: Zerbe O) [M]. New York: Wiley VCH，2003. 439-457.

[52] Lepre C A，Moore J M，Peng J W. Theory and application of NMR-based screening in pharmaceutical research[J]. Chem Rev，2004，104: 3 641-3 676.

[53] Ross A，Senn H. Automation of biomolecular NMR screening[J]. Curr Top Med Chem，2003，3: 55-67.

[54] Hajduk P J，Burns D J. Integration of NMR and high-throughput screening[J]. Comb Chem High T Scr，2002，5: 613-621.

[55] Feng Rei(冯锐)，Xie Hua(谢华)，Ren Da-zhou(任大周). Application of Cryogenic NMR Probes(低温NMR探头的应用)[J]. Chinese J Magn Reson(波谱学杂志)，2002，19: 447-454.

[56] Pervushin K，Riek R，Wider G，et al. Attenuated T2- relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution[J]. Proc Natl Acad Sci USA, 1997，94: 12 366-12 371.

[57] Flaux J，Bertelsen E B，Horwich A L，et al. NMR analysis of a 900K GroEL-GroES complex[J]. Nature，2002，418: 207-211.

[58] Riek R，Wider G，Pervushin K，et al. Polarization transfer by cross-correlated relaxation in solution NMR with very large molecules[J]. Proc Natl Acad Sci USA，1999，96: 4 918-4 923.