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Advance in Structural Bioinformatics pp 49–70Cite as

Quantum Calculation of Protein NMR Chemical Shifts Based on the Automated Fragmentation Method

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 827))

Abstract

The performance of quantum mechanical methods on the calculation of protein NMR chemical shifts is reviewed based on the recently developed automatic fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach. By using the Poisson-Boltzmann (PB) model and first solvation water molecules, the influence of solvent effect is also discussed. Benefiting from the fragmentation algorithm, the AF-QM/MM approach is computationally efficient, linear-scaling with a low pre-factor, and thus can be applied to routinely calculate the ab initio NMR chemical shifts for proteins of any size. The results calculated using Density Functional Theory (DFT) show that when the solvent effect is included, this method can accurately reproduce the experimental 1H NMR chemical shifts, while the 13C NMR chemical shifts are less affected by the solvent. However, although the inclusion of solvent effect shows significant improvement for 15N chemical shifts, the calculated values still have large deviations from the experimental observations. Our study further demonstrates that AF-QM/MM calculated results accurately reflect the dependence of 13Cα NMR chemical shifts on the secondary structure of proteins, and the calculated 1H chemical shift can be utilized to discriminate the native structure of proteins from decoys. 

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References

  1. Bieri M, Kwan AH, Mobli M, King GF, Mackay JP, Gooley PR (2011) Macromolecular NMR spectroscopy for the non-spectroscopist: beyond macromolecular solution structure determination. FEBS J 278:704–715

    Article  CAS  PubMed  Google Scholar 

  2. Kwan AH, Mobli M, Gooley PR, King GF, Mackay JP (2011) Macromolecular NMR spectroscopy for the non-spectroscopist. FEBS J 278:687–703

    Article  CAS  PubMed  Google Scholar 

  3. Cavalli A, Salvatella X, Dobson CM, Vendruscolo M (2007) Protein structure determination from NMR chemical shifts. Proc Natl Acad Sci USA 104:9615–9620

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Lang WH.; Coats JE, Majka J, Hura GL, Lin Y, Rasnik I, McMurray CT (2011) Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops. Proc Natl Acad Sci USA 108:1–8

    Google Scholar 

  5. Selvaratnam R, Chowdhury S, VanSchouwen B, Melacini G (2011) Mapping allostery through the covariance analysis of NMR chemical shifts. Proc Natl Acad Sci USA 108:6133–6138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Shen Y, Lange O, Delaglio F, Rossi P, Aramini JM, Liu G, Eletsky A, Wu Y, Singarapu KK, Lemak A, Ignatchenko A, Arrowsmith CH, Szyperski T, Montelione GT, Baker D, Bax A (2008) Consistent blind protein structure generation from NMR chemical shift data. Proc Natl Acad Sci USA 105:4685–4690

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Wylie BJ, Sperling LJ, Nieuwkoop AJ, Franks WT, Oldfield E, Rienstra CM (2011) Ultrahigh resolution protein structures using NMR chemical shift tensors. Proc Natl Acad Sci USA 108:16974–16979

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Ulmer TS, Ramirez BE, Delaglio F, Bax A (2003) Evaluation of backbone proton positions and dynamics in a small protein by liquid crystal NMR spectroscopy. J Am Chem Soc 125:9179–9191

    Article  CAS  PubMed  Google Scholar 

  9. De Gortari I, Portella G, Salvatella X, Bajaj VS, van der Wel PC, Yates JR, Segall MD, Pickard CJ, Payne MC, Vendruscolo M (2010) Time averaging of NMR chemical shifts in the MLF peptide in the solid state. J Am Chem Soc 132:5993–6000

    Google Scholar 

  10. Sahakyan AB, Vranken WF, Cavalli A, Vendruscolo M (2011) Using side-chain aromatic proton chemical shifts for a quantitative analysis of protein structures. Angew Chem Int Ed 50:9620

    Article  CAS  Google Scholar 

  11. Sahakyan AB, Vranken WF, Cavalli A, Vendruscolo M (2011) Structure-based prediction of methyl chemical shifts in proteins. J Biomol NMR 50:331–346

    Article  CAS  PubMed  Google Scholar 

  12. Helgaker T, Jaszunski M, Ruud K (1999) Ab initio methods for the calculation of NMR shielding and indirect spin-spin coupling constants. Chem Rev 99:293–352

    Article  CAS  PubMed  Google Scholar 

  13. Facelli JC (2011) Chemical shift tensors: theory and application to molecular structural problems. Prog Nucl Magn Reson Spectrosc 58:176–201

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Saito H, Ando I, Ramamoorthy A (2010) Chemical shift tensor—the heart of NMR: insights into biological aspects of proteins. Prog Nucl Magn Reson Spectrosc 57:181–228

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Moon S, Case DA (2007) A new model for chemical shifts of amide hydrogens in proteins. J Biomol NMR 38:139–150

    Google Scholar 

  16. Kohlhoff KJ, Robustelli P, Cavalli A, Salvatella X, Vendruscolo M (2009) Fast and accurate predictions of protein NMR chemical shifts from interatomic distances. J Am Chem Soc 131:13894–13895

    Article  CAS  PubMed  Google Scholar 

  17. Baskaran K, Brunner K, Munte CE, Kalbitzer HR (2010) Mapping of protein structural ensembles by chemical shifts. J Biomol NMR 48:71–83

    Article  CAS  PubMed  Google Scholar 

  18. Han B, Liu Y, Ginzinger SW, Wishart DS (2011) SHIFTX2: significantly improved protein chemical shift prediction. J Biomol NMR 50:43–57

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Sahakyan AB, Vranken WF, Cavalli A, Vendruscolo M (2011) Structure-based prediction of methyl chemical shifts in proteins. J Biomol NMR 50:331

    Google Scholar 

  20. De Dios AC, Pearson JG, Oldfield E (1993) Secondary and tertiary structural effects on protein NMR chemical shifts: an ab initio approach. Science 260:1491–1496

    Article  PubMed  Google Scholar 

  21. De Dios AC (1996) Ab initio calculations of the NMR chemical shift. Prog Nucl Magn Reson Spectrosc 29:229–278

    Article  Google Scholar 

  22. De Dios AC, Pearson JG, Oldfield E (2008) Secondary and tertiary structural effects on protein NMR chemical shifts: an ab initio approach. J. Chem. Phys. 260:1491–1496

    Google Scholar 

  23. Ochsenfeld C, Kussmann J, Koziol F (2004) Ab initio NMR spectra for molecular systems with a thousand and more atoms: a linear scaling method. Angew Chem Int Ed 43:4485–4489

    Article  CAS  Google Scholar 

  24. Oldfield E (2002) Chemical shifts in amino acids, peptides, and proteins: from quantum chemistry to drug design. Ann Rev Phys Chem 53:349–378

    Article  CAS  Google Scholar 

  25. Abildgaard J, Hansen PE, Manalo MN, LiWang A (2009) Deuterium isotope effects on 15 N backbone chemical shifts in proteins. J Biomol NMR 44:119–126

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Tang S, Case DA (2011) Calculation of chemical shift anisotropy in proteins. J Biomol NMR 51:303

    Google Scholar 

  27. Beer M, Kussmann J, Ochsenfeld C (2011) Nuclei-selected NMR shielding calculations: a sublinear-scaling quantum-chemical method. J Chem Phys 134:074102

    Article  PubMed  Google Scholar 

  28. Moon S, Case DA (2006) A comparison of quantum chemical models for calculating NMR shielding parameters in peptides: mixed basis set and ONIOM methods combined with a complete basis set extrapolation. J Comput Chem 27:825–836

    Article  CAS  PubMed  Google Scholar 

  29. Komin S, Gossens C, Tavernelli I, Rothlisberger U, Sebastiani D (2007) NMR solvent shifts of adenine in aqueous solution from hybrid QM/MM molecular dynamics simulations. J Phys Chem B 111:5225–5232

    Article  CAS  PubMed  Google Scholar 

  30. Hinton JF, Guthrie P, Pulay P, Wolinski K (1992) Ab initio quantum mechanical calculation of the chemical shift anisotropy of the hydrogen atom in the (H2O) 17 cluster. J Am Chem Soc 114:1604

    Google Scholar 

  31. Vila JA, Aramini JM, Rossi P, Kuzin A, Su M, Seetharaman J, Xiao R, Tong L, Montelione GT, Scheraga HA (2008) Quantum chemical C-13(alpha) chemical shift calculations for protein NMR structure determination, refinement, and validation. Proc Natl Acad Sci USA 105:14389–14394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Buehl M, Mourik VT (2011) NMR spectroscopy: quantum-chemical calculations, Wires Comput. Mol. Sci. 1:634–647

    Article  Google Scholar 

  33. Mourik VT (2006) Density functional theory reveals an increase in the amino (1)H chemical shift in guanine due to hydrogen bonding with water. J Chem Phys 125:191101

    Google Scholar 

  34. Cui Q, Karplus M (2000) Molecular properties from combined QM/MM methods. 2. Chemical shifts in large molecules. J Phys Chem B 104:3721–3743

    Article  CAS  Google Scholar 

  35. Frank A, Onila I, Möller HM, Exner TE (2011) Toward the quantum chemical calculation of nuclear magnetic resonance chemical shifts of proteins. Proteins 79:2189–2202

    Article  CAS  PubMed  Google Scholar 

  36. Exner TE, Frank A, Onila I, Moeller HM (2012) Toward the quantum chemical calculation of nmr chemical shifts of proteins. 3. conformational sampling and explicit solvents model. J Chem Theory Comput 8:4818–4827

    Article  CAS  Google Scholar 

  37. Frank A, Moeller HM, Exner TE (2012) Toward the quantum chemical calculation of NMR chemical shifts of proteins. 2. Level of theory, basis set, and solvents model dependence. J Chem Theory Comput 8:1480–1492

    Article  CAS  Google Scholar 

  38. Gao Q, Yokojima S, Kohno T, Ishida T, Fedorov DG, Kitaura K, Fujihira M, Nakamura S (2007) Ab initio NMR chemical shift calculations on proteins using fragment molecular orbitals with electrostatic environment. Chem Phys Lett 445:331–339

    Article  CAS  Google Scholar 

  39. Gao Q, Yokojima S, Fedorov DG, Kitaura K, Sakurai M, Nakamura S (2010) Fragment-molecular-orbital-method-based ab initio NMR chemical-shift calculations for large molecular systems. J Chem Theory Comput 6:1428–1444

    Article  CAS  Google Scholar 

  40. Zhu T, He Xiao, Zhang JZH (2012) Fragment density functional theory calculation of NMR chemical shifts for proteins with implicit solvation. Phys Chem Chem Phys 14:7837–7845

    Article  CAS  PubMed  Google Scholar 

  41. He X, Wang B, Merz KM (2009) Protein NMR chemical shift calculations based on the automated fragmentation QM/MM approach. J Phys Chem B 113:10380–10388

    Article  CAS  PubMed  Google Scholar 

  42. Mogelhoj A, Aidas K, Mikkelsen KV, Kongsted J (2008) Solvent effects on the nitrogen NMR shielding and nuclear quadrupole coupling constants in 1-methyltriazoles. Chem Phys Lett 460:129–136

    Article  CAS  Google Scholar 

  43. Kitevski-LeBlanc JL, Evanics F, Prosser RS (2009) Approaches for the measurement of solvent exposure in proteins by 19F NMR. J Biomol NMR 45:255–264

    Article  CAS  PubMed  Google Scholar 

  44. Dracinsky M, Bour P (2010) Computational analysis of solvent effects in NMR spectroscopy. J Chem Theory Comput 6:288–299

    Article  CAS  Google Scholar 

  45. Witanowski M, Biedrzycka Z, Sicinska W, Grabowski Z (1998) A study of solvent polarity and hydrogen bonding effects on the nitrogen NMR shielding of isomeric tetrazoles and ab initio calculation of the nitrogen shielding of azole systems. J Magn Reson 131:54–60

    Article  CAS  PubMed  Google Scholar 

  46. Witanowski M, Sicinska W, Biedrzycka Z, Webb GA (1996) Solvent effects on the nitrogen NMR shieldings of cyanamide and N,N-dimethyl cyanamide. J Mol Struc 380:133

    Google Scholar 

  47. Mennucci B, Martinez JM, Tomasi J (2001) Solvent effects on nuclear shieldings: continuum or discrete solvation models to treat hydrogen bond and polarity effects? J Phys Chem A 105:7287–7296

    Article  CAS  Google Scholar 

  48. Tang M, Sperling LJ, Berthold DA, Schwieters CD, Nesbitt AE, Nieuwkoop AJ, Gennis RB, Rienstra CM (2011) High-resolution membrane protein structure by joint calculations with solid-state NMR and X-ray experimental data. J Biomol NMR 51:227–233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Zhu T, Zhang JZH, He X (2013) Automated fragmentation QM/MM calculation of amide proton chemical shifts in proteins with explicit solvent model. J Chem Theory Comput 9:2104–2114

    Article  CAS  Google Scholar 

  50. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JAJ, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamao C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski, JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL. Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople J (2010) Gausian09, revision B.01, Gaussian, Inc., Wallingford, CT

    Google Scholar 

  51. Dixon SL, van der Vaart A, Gogonea V, Vincent M, Brothers EN, Suarez D, Westerhoff LM, Jr. Merz KM (1999) DivCon. The Pennsylvania State University, University Park, PA

    Google Scholar 

  52. Imai T, Hiraoka R, Kovalenko A, Hirata F (2007) Locating missing water molecules in protein cavities by the three-dimensional reference interaction site model theory of molecular solvation. Proteins 66:804–813

    Article  CAS  PubMed  Google Scholar 

  53. Yoshida N, Phongphanphanee S, Maruyama Y, Imai T, Hirata F (2006) Selective ion-binding by protein probed with the 3D-RISM theory. J Am Chem Soc 128:12042–12043

    Article  CAS  PubMed  Google Scholar 

  54. De Simone A, Cavalli A, Hsu S-TD, Vranken W, Vendruscolo M (2009) Accurate random coil chemical shifts from an analysis of loop regions in native states of proteins. J Am Chem Soc 131:16332

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grants No. 10974054, 20933002 and 21303057) and Shanghai PuJiang program (09PJ1404000). X.H. is also supported by the Specialized Research Fund for Doctoral Program of Higher Education (Grant No. 20130076120019) and the Fundamental Research Funds for the Central Universities. We thank the Supercomputer Center of East China Normal University for providing us computational time. X.H. also gratefully acknowledges many helpful discussions with Kenneth Merz, Bing Wang, Ning Liao, David Case and Sishi Tang.

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Authors and Affiliations

  1. State Key Laboratory of Precision Spectroscopy and Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, China

    Tong Zhu, John Z. H. Zhang & Xiao He

  2. Department of Chemistry, New York University, New York, 10003, NY, USA

    John Z. H. Zhang

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  1. Tong Zhu
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Correspondence to Xiao He .

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  1. Shanghai JiaoTong University, Shanghai, China

    Dongqing Wei

  2. Shanghai Jiao Tong University, Shanghai, China

    Qin Xu

  3. Shanghai Jiao Tong University, Shanghai, China

    Tangzhen Zhao

  4. Shanghai Jiao Tong University, Shanghai, China

    Hao Dai

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Zhu, T., Zhang, J.Z.H., He, X. (2015). Quantum Calculation of Protein NMR Chemical Shifts Based on the Automated Fragmentation Method. In: Wei, D., Xu, Q., Zhao, T., Dai, H. (eds) Advance in Structural Bioinformatics. Advances in Experimental Medicine and Biology, vol 827. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9245-5_5

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