Skip to main content

Advertisement

SpringerLink
Log in

AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules

  • Article
  • Published:
Journal of Biomolecular NMR Aims and scope Submit manuscript

Abstract

We evaluate the performance of the automated fragmentation quantum mechanics/molecular mechanics approach (AF-QM/MM) on the calculation of protein and nucleic acid NMR chemical shifts. The AF-QM/MM approach models solvent effects implicitly through a set of surface charges computed using the Poisson–Boltzmann equation, and it can also be combined with an explicit solvent model through the placement of water molecules in the first solvation shell around the solute; the latter substantially improves the accuracy of chemical shift prediction of protons involved in hydrogen bonding with solvent. We also compare the performance of AF-QM/MM on proteins and nucleic acids with two leading empirical chemical shift prediction programs SHIFTS and SHIFTX2. Although the empirical programs outperform AF-QM/MM in predicting chemical shifts, the differences are in some cases small, and the latter can be applied to chemical shifts on biomolecules which are outside the training set employed by the empirical programs, such as structures containing ligands, metal centers, and non-standard residues. The AF-QM/MM described here is implemented in version 5 of the SHIFTS software, and is fully automated, so that only a structure in PDB format is required as input.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17

Similar content being viewed by others

References

  • Arnold WD, Oldfield E (2000) The chemical nature of hydrogen bonding in proteins via NMR: J-couplings, chemical shifts, and AIM theory. J Am Chem Soc 122:12835–12841

    Article  Google Scholar 

  • Case DA (2013) Chemical shifts in biomolecules. Curr Opin Struct Biol 23:172–176

    Article  Google Scholar 

  • Case DA, Babin V, Berryman JT, Betz RM, Cai Q, Cerutti DS, Cheatham TE III, Darden TA, Duke RE, Gohlke H, Goetz AW, Gusarov S, Homeyer N, Janowski P, Kaus J, Kolossváry I, Kovalenko A, Lee TS, LeGrand S, Luchko T, Luo R, Madej B, Merz KM, Paesani F, Roe DR, Roitberg A, Sagui C, Salomon-Ferrer R, Seabra G, Simmerling CL, Smith W, Swails J, Walker RC, Wang J, Wolf RM, Wu X, Kollman PA (2014) AMBER 14. University of California, San Francisco

    Google Scholar 

  • 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  ADS  Google Scholar 

  • Chien CY, Tejero R, Huang YP, Zimmerman DE, Rios CB, Krug RM, Montelione GT (1997) A novel RNA-binding motif in influenza A virus non-structural protein 1. Nat Struct Biol 4:891–895

    Article  Google Scholar 

  • Cromsigt J, Hilbers CW, Wijmenga SS (2001) Prediction of proton chemical shifts in RNA—their use in structure refinement and validation. J Biomol NMR 21:11–29

    Article  Google Scholar 

  • 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  Google Scholar 

  • 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  ADS  Google Scholar 

  • Dracinsky M, Möller HM, Exner TE (2013) Conformational sampling by Ab initio molecular dynamics simulations improves NMR chemical shift predictions. J Chem Theory Comput 9:3806–3815

    Article  Google Scholar 

  • Exner TE, Frank A, Onila I, Möller 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  Google Scholar 

  • Flaig D, Beer M, Ochsenfeld C (2012) Convergence of electronic structure with the size of the QM region: example of QM/MM NMR shieldings. J Chem Theory Comput 8:2260–2271

    Article  Google Scholar 

  • Flaig D, Maurer M, Hanni M, Braunger K, Kick L, Thubauville M, Ochsenfeld C (2014) Benchmarking hydrogen and carbon NMR chemical shifts at HF, DFT, and MP2 levels. J Chem Theory Comput 10:572–578

    Article  Google Scholar 

  • 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  Google Scholar 

  • Frank AT, Bae S-H, Stelzer AC (2013) Prediction of RNA H-1 and C-13 chemical shifts: a structure based approach. J Phys Chem B 117:13497–13506

    Article  Google Scholar 

  • Frisch MJ, T 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) Gaussian 09 revision B.01 Gaussian Inc. Wallingford CT

  • 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  ADS  Google Scholar 

  • 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  Google Scholar 

  • Garcia FL, Szyperski T, Dyer JH, Choinowski T, Seedorf U, Hauser H, Wuthrich K (2000) NMR structure of the sterol carrier protein-2: implications for the biological role. J Mol Biol 295:595–603

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Hartman JD, Beran GJO (2014) Fragment-based electronic structure approach for computing nuclear magnetic resonance chemical shifts in molecular crystals. J Chem Theory Comput 10:4862–4872

    Article  Google Scholar 

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

    Article  Google Scholar 

  • He X, Zhu T, Wang XW, Liu JF, Zhang JZH (2014) Fragment quantum mechanical calculation of proteins and its applications. Acc Chem Res 47:2748–2757

    Article  Google Scholar 

  • 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  Google Scholar 

  • 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  Google Scholar 

  • Ji C, Mei Y, Zhang JZH (2008) Developing polarized protein-specific charges for protein dynamics: MD free energy calculation of pK(a) shifts for Asp(26)/Asp(20) in thioredoxin. Biophys J 95:1080–1088

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • Krylov AI, Gill PMW (2013) Q-Chem: an engine for innovation. WIREs Comput Mol Sci 3:317–326

    Article  Google Scholar 

  • Li DW, Brüschweiler R (2012) PPM: a side-chain and backbone chemical shift predictor for the assessment of protein conformational ensembles. J Biomol NMR 54:257–265

    Article  Google Scholar 

  • Liu B, Shadrin A, Sheppard C, Mekler V, Xu Y, Severinov K, Matthews S, Wigneshweraraj S (2014) A bacteriophage transcription regulator inhibits bacterial transcription initiation by Sigma-factor displacement. Nucleic Acids Res 42:4294–4305

    Article  Google Scholar 

  • Meiler J, Baker D (2003) Rapid protein fold determination using unassigned NMR data. Proc Natl Acad Sci USA 100:15404–15409

    Article  ADS  Google Scholar 

  • 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  Google Scholar 

  • Neese F (2012) The ORCA program system. WIREs Comput Mol Sci 2:73–78

    Article  Google Scholar 

  • Nozinovic S, Fuertig B, Jonker HRA, Richter C, Schwalbe H (2010) High-resolution NMR structure of an RNA model system: the 14-mer cUUCGg tetraloop hairpin RNA. Nucl Acids Res 38:683–694

    Article  Google Scholar 

  • 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 50:9620–9623

    Article  Google Scholar 

  • Salomon-Ferrer R, Case DA, Walker RC (2013) An overview of the Amber biomolecular simulation package. WIREs Comput Mol Sci 3:198–210

    Article  Google Scholar 

  • Schafer A, Huber C, Ahlrichs R (1994) Fully optimized contracted gaussian-basis sets of triple zeta valence quality for atoms Li to Kr. J Chem Phys 100:5829–5835

    Article  ADS  Google Scholar 

  • Scheurer C, Skrynnikov NR, Lienin SF, Straus SK, Bruschweiler R, Ernst RR (1999) Effects of dynamics and environment on N-15 chemical shielding anisotropy in proteins. A combination of density functional theory, molecular dynamics simulation, and NMR relaxation. J Am Chem Soc 121:4242–4251

    Article  Google Scholar 

  • Shao Y, Molnar LF, Jung Y, Kussmann J, Ochsenfeld C, Brown ST, Gilbert ATB, Slipchenko LV, Levchenko SV, O’Neill DP, DiStasio RA Jr, Lochan RC, Wang T, Beran GJO, Besley NA, Herbert JM, Lin CY, Van Voorhis T, Chien SH, Sodt A, Steele RP, Rassolov VA, Maslen PE, Korambath PP, Adamson RD, Austin B, Baker J, Byrd EFC, Dachsel H, Doerksen RJ, Dreuw A, Dunietz BD, Dutoi AD, Furlani TR, Gwaltney SR, Heyden A, Hirata S, Hsu C-P, Kedziora G, Khalliulin RZ, Klunzinger P, Lee AM, Lee MS, Liang W, Lotan I, Nair N, Peters B, Proynov EI, Pieniazek PA, Rhee YM, Ritchie J, Rosta E, Sherrill CD, Simmonett AC, Subotnik JE, Woodcock HL III, Zhang W, Bell AT, Chakraborty AK, Chipman DM, Keil FJ, Warshel A, Hehre WJ, Schaefer HF III, Kong J, Krylov AI, Gill PMW (2006) Head-Gordon MAdvances in methods and algorithms in a modern quantum chemistry program package. Phys Chem Chem Phys 8:3172–3191

    Article  Google Scholar 

  • 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  ADS  Google Scholar 

  • Shen Y, Vernon R, Baker D, Bax A De (2009) novo protein structure generation from incomplete chemical shift assignments. J Biomol NMR 43:63–78

    Article  Google Scholar 

  • Sindhikara DJ, Yoshida N, Hirata F (2012) Placevent: an algorithm for prediction of explicit solvent atom distributionuApplication to HIV-1 protease and F-ATP synthase. J Comput Chem 33:1536–1543

    Article  Google Scholar 

  • Sitkoff D, Case DA (1997) Density-functional calculations of proton chemical shifts in model peptides and applications to proteins. Abstr Papers Am Chem Soc 214:234-PHYS

    Google Scholar 

  • Song J, Ji C, Zhang JZH (2013) The critical effect of polarization on the dynamical structure of guanine quadruplex DNA. Phys Chem Chem Phys 15:3846–3854

    Article  Google Scholar 

  • Sumowski CV, Hanni M, Schweizer S, Ochsenfeld C (2014) Sensitivity of ab initio vs empirical methods in computing structural effects on nmr chemical shifts for the example of peptides. J Chem Theory Comput 10:122–133

    Article  Google Scholar 

  • Tang S, Case DA (2011) Calculation of chemical shift anisotropy in proteins. J Biomol NMR 51:303–312

    Article  Google Scholar 

  • Victora A, Möller HM, Exner TE (2014) Accurate ab initio prediction of NMR chemical shifts of nucleic acids and nucleic acids/protein complexes. Nucl Acids Res 42:e173

    Article  Google Scholar 

  • Wang B, Brothers EN, van der Vaart A, Merz KM (2004) Fast semiempirical calculations for nuclear magnetic resonance chemical shifts: a divide-and-conquer approach. J Chem Phys 120:11392–11400

    Article  ADS  Google Scholar 

  • Wang B, He X, Merz KM (2013) Quantum mechanical study of vicinal J spin-spin coupling constants for the protein backbone. J Chem Theory Comput 9:4653–4659

    Article  Google Scholar 

  • Wijmenga SS, Kruithof M, Hilbers CW (1997) Analysis of H-1 chemical shifts in DNA: assessment of the reliability of H-1 chemical shift calculations for use in structure refinement. J Biomol NMR 10:337–350

    Article  Google Scholar 

  • Williamson MP, Craven CJ (2009) Automated protein structure calculation from NMR data. J Biomol NMR 43:131–143

    Article  Google Scholar 

  • Xu XP, Case DA (2001) Automated prediction of (15)N, (13)C(alpha), (13)C(beta) and (13)C chemical shifts in proteins using a density functional database. J Biomol NMR 21:321–333

    Article  Google Scholar 

  • 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  Google Scholar 

  • Zhang Y, Wu AN, Xu X, Yan YJ (2006) OPBE: a promising density functional for the calculation of nuclear shielding constants. Chem Phys Lett 421:383–388

    Article  ADS  Google Scholar 

  • Zhu T, He X, 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  Google Scholar 

  • 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  Google Scholar 

  • Zhu T, Zhang JZH, He X (2014) Correction of erroneously packed protein’s side chains in the NMR structure based on ab initio chemical shift calculations. Phys Chem Chem Phys 16:18163–18169

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the US National Institutes of Health (GM45811) and by the National Natural Science Foundation of China (Grants No. 21303057, 21403068), the Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20130076120019) and the Fundamental Research Funds for the Central Universities of China.

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University, Piscataway, NJ, 08854, USA

    Jason Swails & David A. Case

  2. State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, 200062, China

    Tong Zhu & Xiao He

  3. NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, 200062, China

    Xiao He

Authors
  1. Jason Swails
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David A. Case
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiao He or David A. Case.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Swails, J., Zhu, T., He, X. et al. AFNMR: automated fragmentation quantum mechanical calculation of NMR chemical shifts for biomolecules. J Biomol NMR 63, 125–139 (2015). https://doi.org/10.1007/s10858-015-9970-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10858-015-9970-3

Keywords

Search

Navigation