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Validation of the GROMOS force-field parameter set 45A3 against nuclear magnetic resonance data of hen egg lysozyme

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Abstract

The quality of molecular dynamics (MD) simulations of proteins depends critically on the biomolecular force field that is used. Such force fields are defined by force-field parameter sets, which are generally determined and improved through calibration of properties of small molecules against experimental or theoretical data. By application to large molecules such as proteins, a new force-field parameter set can be validated. We report two 3.5 ns molecular dynamics simulations of hen egg white lysozyme in water applying the widely used GROMOS force-field parameter set 43A1 and a new set 45A3. The two MD ensembles are evaluated against NMR spectroscopic data NOE atom–atom distance bounds, 3JNH α and 3Jαβ coupling constants, and 15N relaxation data. It is shown that the two sets reproduce structural properties about equally well. The 45A3 ensemble fulfills the atom–atom distance bounds derived from NMR spectroscopy slightly less well than the 43A1 ensemble, with most of the NOE distance violations in both ensembles involving residues located in loops or flexible regions of the protein. Convergence patterns are very similar in both simulations atom-positional root-mean-square differences (RMSD) with respect to the X-ray and NMR model structures and NOE inter-proton distances converge within 1.0–1.5 ns while backbone 3JHNα-coupling constants and 1H– 15N order parameters take slightly longer, 1.0–2.0 ns. As expected, side-chain 3Jαβ-coupling constants and 1H– 15N order parameters do not reach full convergence for all residues in the time period simulated. This is particularly noticeable for side chains which display rare structural transitions. When comparing each simulation trajectory with an older and a newer set of experimental NOE data on lysozyme, it is found that the newer, larger, set of experimental data agrees as well with each of the simulations. In other words, the experimental data converged towards the theoretical result.

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References

  • I. Antes W. Thiel W.F. Gunsteren Particlevan (2002) Eur. Biophys. J. 31 504–520

    Google Scholar 

  • D. Bakowies W.F. Gunsteren Particlevan (2002) J. Mol. Biol. 315 713–736

    Google Scholar 

  • H.J.C. Berendsen J.P.M. Postma W.F. Van Gunsteren A. Dinola J.R. Haak (1984) J. Chem. Phys. 81 3684–3690

    Google Scholar 

  • Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F. and Hermans, J. (1981) In Intermolecular Forces, Pullman, B. (Ed.), Reidel, Dordrecht, pp. 331–342.

  • A.M. Bonvin M. Sunnerhagen G. Otting W.F. Gunsteren Particlevan (1998) J. Mol. Biol. 282 859–873

    Google Scholar 

  • B.R. Brooks R.E. Bruccoleri B.D. Olafson D.J. States S. Swaminathan M. Karplus (1983) J. Comput. Chem. 4 187–217

    Google Scholar 

  • M. Buck D.B. Boyd C. Redfield D.A. MacKenzie D.J. Jeenes D.B. Archer C.M. Dobson (1995) Biochemistry 34 4041–4055

    Google Scholar 

  • Carter, D., He, J., Ruble, J.R. and Wright, B. (1997) Protein Data Bank, entry 1AKI.

  • I. Chandrasekhar W.F. Gunsteren Particlevan (2001) Curr. Sci. 81 1325–1327

    Google Scholar 

  • I. Chandrasekhar W.F. Gunsteren Particlevan (2002) Eur. Biophys. J. 31 89–101

    Google Scholar 

  • I. Chandrasekhar M.A. Kastenholz R.D. Lins C. Oostenbrink L.D. Schuler D.P. Tieleman W.F. Gunsteren Particlevan (2003) Eur. Biophys. J. 32 67–77

    Google Scholar 

  • W. Czechtizky X. Daura A. Vasella W.F. Gunsteren Particlevan (2001) Helv. Chim. Acta 84 2132–2145

    Google Scholar 

  • X. Daura K. Gademann B. Jaun D. Seebach W.F. van Gunsteren A.E. Mark (1999) Angew. Chem. Ind. Ed. 38 236–240

    Google Scholar 

  • X. Daura A. Glättli P. Gee C. Peter W.F. Gunsteren Particlevan (2002) Adv. Protein Chem. 62 341–360

    Google Scholar 

  • X. Daura A.E. Mark W.F. Gunsteren Particlevan (1998) J. Comput. Chem. 19 535–547

    Google Scholar 

  • X. Daura W.F. Gunsteren Particlevan D. Rigo B. Jaun D. Seebach (1997) Chem.-Eur. J. 3 1410–1417

    Google Scholar 

  • A. DeMarco M. Llinas K. Wüthrich (1978) Biopolymers >17 617–636

    Google Scholar 

  • E. Egberts S.-J. Marrink H.J.C. Berendsen (1994) Eur. Biophys. J. 22 423–436

    Google Scholar 

  • A. Glättli X. Daura W.F. Gunsteren Particlevan (2002) J. Chem. Phys. 116 9811–9828

    Google Scholar 

  • J. Hermans H.J.C. Berendsen W.F. Gunsteren Particlevan J.P.M. Postma (1984) Biopolymers 23 1513–1518

    Google Scholar 

  • Hünenberger, P.H. and van Gunsteren, W.F. (1997) In Computer Simulation of Biomolecular Systems, Theoretical and Experimental Applications, Vol. 3, van Gunsteren, W.F., Weiner, P.K. and Wilkinson, A.J. (Eds.), Kluwer Academic Publishers, Dordrecht, pp. 3–82.

  • P.H. Hünenberger A.E. Mark W.F. Gunsteren Particlevan (1995) J. Mol. Biol. 252 492–502

    Google Scholar 

  • W.L. Jorgensen J. Tirado-Rives (1988) J. Am. Chem. Soc. 110 1657–1666

    Google Scholar 

  • W. Kabsch C. Sander (1983) Biopolymers 22 2577–2637

    Google Scholar 

  • M. Karplus (1959) J. Chem. Phys. 30 11–15

    Google Scholar 

  • M. Karplus J.A. McCammon (2002) Nat. Struct. Biol. 9 646–652

    Google Scholar 

  • M. Levitt (1983) J. Mol. Biol. 168 595–620

    Google Scholar 

  • M. Levitt M. Hirshberg R. Sharon V. Daggett (1995) Comput. Phys. Commun 91 215–231

    Google Scholar 

  • A.D. MacKerell SuffixJr. J. Wiorkiewiczkuczera M. Karplus (1995) J. Am. Chem. Soc. 117 11946–11975

    Google Scholar 

  • J.L. Markley A. Bax Y. Arata C.W. Hilbers R. Kaptein B.D. Sykes P.E. Wright K. Wüthrich (1998) J. Biomol. NMR 12 1–23

    Google Scholar 

  • F.A. Momany R. Rone (1992) J. Comput. Chem. 13 888–900

    Google Scholar 

  • G. Nemethy K.D. Gibson K.A. Palmer C.N. Yoon G. Paterlini A. Zagari S. Rumsey H. A. Scheraga (1992) J. Phys. Chem. 96 6472–6484

    Google Scholar 

  • B.C. Oostenbrink J.W. Pitera M.M.H. Lipzig ParticleVan J.H.N. Meerman W.F. Gunsteren Particlevan (2000) J. Med. Chem. 43 4594–4605

    Google Scholar 

  • A. Pardi M. Billeter K. Wüthrich (1984) J. Mol. Biol. 180 741–751

    Google Scholar 

  • D.A. Pearlman D.A. Case J.W. Caldwell W.S. Ross T.E. Cheatham SuffixIII S. DeBolt D. Ferguson G. Seibel P.A. Kollman (1995) Comput. Phys. Commun 91 1–41

    Google Scholar 

  • J.-P. Ryckaert G. Ciccotti H.J.C. Berendsen (1977) J. Comput. Phys. 23 327–341

    Google Scholar 

  • L.D. Schuler W.F. Gunsteren Particlevan (2000) Mol. Sim. 25 301–319

    Google Scholar 

  • L.D. Schuler X. Daura W.F. Gunsteren Particlevan (2001) J. Comput. Chem. 22 1205–1218

    Google Scholar 

  • H. Schwalbe S.B. Grimshaw A. Spencer M. Buck J. Boyd C.M. Dobson C. Redfield L. Smith (2001) Protein Sci. 10 677–688

    Google Scholar 

  • W.R.P. Scott P.H. Hünenberger I.G. Tironi A.E. Mark S.R. Billeter J. Fennen A.E. Torda P. Huber P. Krüger W.F. Gunsteren Particlevan (1999) J. Phys. Chem. A 103 3596–3607

    Google Scholar 

  • L.J. Smith C.M. Dobson W.F. Gunsteren Particlevan (1996) J. Mol. Biol. 286 1567–1580

    Google Scholar 

  • L.J. Smith C.M. Dobson W.F. Gunsteren Particlevan (1999) Proteins 36 77–86

    Google Scholar 

  • L.J. Smith A.E. Mark C.M. Dobson W.F. Gunsteren Particlevan (1995) Biochemistry 34 10918–10931

    Google Scholar 

  • L.J. Smith M.J. Sutcliffe C. Redfield C.M. Dobson (1991) Biochemistry 30 986–996

    Google Scholar 

  • L.J. Smith M.J. Sutcliffe C. Redfield C.M. Dobson (1993) J. Mol. Biol. 229 930–944

    Google Scholar 

  • U. Stocker W.F. Gunsteren Particlevan (2000) Proteins 40 145–153

    Google Scholar 

  • U. Stocker K. Spiegel W.F. Gunsteren Particlevan (2000) J. Biomol. NMR 18 1–12

    Google Scholar 

  • J. Tropp (1980) J. Chem. Phys. 72 6035–6043

    Google Scholar 

  • W.F. Gunsteren Particlevan H.J.C. Berendsen (1987) Groningen Molecular Simulation (GROMOS) Library Manual Biomos Groningen

    Google Scholar 

  • W.F. Gunsteren Particlevan H.J.C. Berendsen (1990) Angew. Chem. Int. Ed. 29 992–1023

    Google Scholar 

  • W.F. Gunsteren Particlevan A.E. Mark (1998) J. Chem. Phys. 108 6109–6116

    Google Scholar 

  • W.F. Gunsteren Particlevan S.R. Billeter A.A. Eising P.H. Hünenberger P. Krüger A.E. Mark W.R.P. Scott I.G. Tironi (1996) Biomolecular Simulation: The GROMOS96 Manual and User Guide Vdf Hochschulverlag AG an der ETH Zürich Zürich

    Google Scholar 

  • van Gunsteren, W.F., Bonvin, A.M.J.J., Daura, X. and Smith, L.J. (1999) In Structure, Computation and Dynamics in Protein NMR. Biol. Magnetic Resonance, Vol. 17, Krishna, K.N. and Berliner, L.J. (Eds.), Plenum Publishers, New York, pp. 3–35.

  • W.F. Gunsteren Particlevan R. Bürgi C. Peter X. Daura (2001) Angew. Chem. Int. Ed. 40 351–355

    Google Scholar 

  • van Gunsteren, W.F., Daura, X. and Mark, A.E. (1998) In Encyclopedia of Computational Chemistry, Vol. 2, von Ragué Schleyer, P. (Ed.), John Wiley & Sons, New York, pp. 1211–1216.

  • P.K. Weiner P.A. Kollman (1981) J. Comput. Chem. 2 287–303

    Google Scholar 

  • K. Wüthrich M. Billeter W. Braun (1983) J. Mol. Biol. 169 949–961

    Google Scholar 

Download references

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Authors and Affiliations

  1. Laboratory of Physical Chemistry, ETH Hönggerberg Zürich, 8093, Zürich, Switzerland

    T. A. Soares, C. Oostenbrink & W. F. van Gunsteren

  2. InstitucióCatalana de Recerca i Estudis Avancats and Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Spain

    X. Daura

  3. Oxford Centre for Molecular Sciences, Central Chemistry Laboratory, University of Oxford, Oxford, United Kingdom

    L. J. Smith

Authors
  1. T. A. Soares
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  2. X. Daura
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  3. C. Oostenbrink
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  4. L. J. Smith
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  5. W. F. van Gunsteren
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Correspondence to W. F. van Gunsteren.

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Soares, T.A., Daura, X., Oostenbrink, C. et al. Validation of the GROMOS force-field parameter set 45A3 against nuclear magnetic resonance data of hen egg lysozyme. J Biomol NMR 30, 407–422 (2004). https://doi.org/10.1007/s10858-004-5430-1

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