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Definition and testing of the GROMOS force-field versions 54A7 and 54B7

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Abstract

New parameter sets of the GROMOS biomolecular force field, 54A7 and 54B7, are introduced. These parameter sets summarise some previously published force field modifications: The 53A6 helical propensities are corrected through new φ/ψ torsional angle terms and a modification of the N–H, C=O repulsion, a new atom type for a charged −CH3 in the choline moiety is added, the Na+ and Cl− ions are modified to reproduce the free energy of hydration, and additional improper torsional angle types for free energy calculations involving a chirality change are introduced. The new helical propensity modification is tested using the benchmark proteins hen egg-white lysozyme, fox1 RNA binding domain, chorismate mutase and the GCN4-p1 peptide. The stability of the proteins is improved in comparison with the 53A6 force field, and good agreement with a range of primary experimental data is obtained.

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Abbreviations

CM:

Chorismate mutase

FOX:

Fox1 RNA binding domain

GCN:

GCN4-p1 peptide

HEWL:

Hen egg-white lysozyme

PDB:

Protein Data Bank

RMSD:

Root-mean-square deviation

SPC:

Simple point charge

References

  • Artymiuk PJ, Blake CCF, Rice DW, Wilson KS (1982) The structures of the monoclinic and orthorhombic forms of hen egg-white lysozyme at 6 angstroms resolution. Acta Crystallogr Sect B 38:778–783

    Google Scholar 

  • Auweter SD, Fasan R, Reymond L, Underwood JG, Black DL, Pitsch S, Allain FH (2006) Molecular basis of RNA recognition by the human alternative splicing factor Fox-1. Embo J 25:163–173

    Article  PubMed  CAS  Google Scholar 

  • Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) In: Pullman B et al (eds) Intermolecular forces. Reidel, Dordrecht, The Netherlands, pp 331–342

  • Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684–3690

    Article  CAS  Google Scholar 

  • Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) Charmm—a program for macromolecular energy, minimization and dynamics calculations. J Comput Chem 4:187–217

    Article  CAS  Google Scholar 

  • Cao Z, Lin Z, Wang J, Liu H (2009) Refining the description of peptide backbone conformations improves protein simulations using the GROMOS 53A6 force field. J Comput Chem 30:645–660

    Article  PubMed  CAS  Google Scholar 

  • Christen M, Hünenberger PH, Bakowies D, Baron R, Bürgi R, Geerke DP, Heinz TN, Kastenholz MA, Kräutler V, Oostenbrink C, Peter C, Trzesniak D, van Gunsteren WF (2005) The GROMOS software for biomolecular simulation: GROMOS05. J Comput Chem 26:1719–1751

    Article  PubMed  CAS  Google Scholar 

  • Cornell WD, Cieplak P, Bayly CI, Gould IR, Mertz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1995) A second generation force field for the simulation of proteins, nucleic acids and organic molecules. J Am Chem Soc 117:5179–5197

    Article  CAS  Google Scholar 

  • Daura X, Mark AE, van Gunsteren WF (1998) Parametrization of aliphatic CHn united atoms of GROMOS96 force field. J Comput Chem 19:535–547

    Article  CAS  Google Scholar 

  • Dolenc J, Missimer JH, Steinmetz MO, van Gunsteren WF (2010) Methods of NMR structure refinement: molecular dynamics simulations improve the agreement with measured NMR data of a C-terminal peptide of GCN4-p1. J Biomol NMR 47:221–235

    Article  PubMed  CAS  Google Scholar 

  • Eichenberger AP, Gattin Z, Yalak G, van Gunsteren WF (2010) Molecular dynamics simulation of ester-linked hen egg white lysozyme reveals the effect of missing backbone hydrogen-bond donors on the protein structure. Helv Chim Acta 93:1857–1869

    Article  CAS  Google Scholar 

  • Fletcher CM, Jones DN, Diamond R, Neuhaus D (1996) Treatment of NOE constraints involving equivalent or nonstereoassigned protons in calculations of biomacromolecular structures. J Biomol NMR 169:292–310

    Article  Google Scholar 

  • Glättli A, van Gunsteren WF (2004) Are NMR-derived model structures for peptides representative for the ensemble of structures adopted in solution? Probing the fourth helical secondary structure of beta-peptides by molecular dynamics simulation. Angew Chem 116:6472–6476

    Article  Google Scholar 

  • Heinz TN, van Gunsteren WF, Huenenberger PH (2001) Comparison of four methods to compute the dielectric permittivity of liquids from molecular dynamics simulations. J Chem Phys 115:1125–1135

    Article  CAS  Google Scholar 

  • Humphrey W, Dalke A, Schulten K (1996) VMD—visual molecular dynamics. J Mol Graph 14:33–38

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen WL, Tirado-Rives J (1988) The OPLS potential functions for proteins—energy minimizations for crystals of cyclic peptides and crambin. J Am Chem Soc 110:1657–1666

    Article  CAS  Google Scholar 

  • Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118:11225–11236

    Article  CAS  Google Scholar 

  • Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637

    Article  PubMed  CAS  Google Scholar 

  • Karplus M (1959) Interpretation of the electron-spin resonance spectrum of the methyl radical. J. Chem. Phys. 30:11–15

    Article  CAS  Google Scholar 

  • MacKerell AD Jr, Wiórkiewicz-Kuczera J, Karplus M (1995) An all-atom empirical energy function for the simulation of nucleicacids. J Am Chem Soc 117:11946–11975

    Article  CAS  Google Scholar 

  • MacKerell AD Jr, Bashford D, Bellot M, Dunbrack RL Jr, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE III, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  • Okvist M, Dey R, Sasso S, Grahn E, Kast P, Krengel U (2006) 1.6Å crystal structure of the secreted chorismate mutase from mycobacterium tuberculosis. Novel Fold Topol Reveal 357:1483–1499

    Google Scholar 

  • Oostenbrink C, Villa A, Mark AE, van Gunsteren WF (2004) A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem 25:1656

    Article  PubMed  CAS  Google Scholar 

  • Oostenbrink C, Soares TA, van der Vegt NFA, van Gunsteren WF (2005) Validation of the 53A6 GROMOS force field. Eur Biophys J 34:273–284

    Article  PubMed  CAS  Google Scholar 

  • Pardi A, Billeter M, Wüthrich K (1984) Calibration of the angular dependence of the amide proton-c alpha proton coupling constants, 3 J HN − α, in a globular protein. use of 3 J HN − α for identification of helical secondary structure. J Mol Biol 180:741–751

    Google Scholar 

  • Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE III, DeBolt S, Ferguson D, Seibel G, Kollman PA (1995) Amber, a package of computer-programs for applying molecular mechanics, normal-mode analysis, moleculardynamics and free-energy calculations to simulate the structural and energetic properties of molecules. Comput Phys Commun 91:1–41

    Article  CAS  Google Scholar 

  • Poger D, van Gunsteren WF, Mark AE (2010) A new force field for simulating phosphatidylcholine bilayers. J Comput Chem 31:1117–1125

    Article  PubMed  CAS  Google Scholar 

  • Reif M, Hünenberger PH (2010) Computation of methodology-independent single-ion solvation properties from molecular simulations. IV. Optimised Lennard–Jones interaction parameter sets for the alkali and halide ions in water. J Chem Phys 134:144104–144125

    Google Scholar 

  • Ryckaert J-P, Ciccotti G, Berendsen HJC (1977) Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 23:327–341

    Article  CAS  Google Scholar 

  • Schuler LD, Daura X, van Gunsteren WF (2001) An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J Comput Chem 22:1205–1218

    Article  CAS  Google Scholar 

  • Schwalbe H, Grimshaw SB, Spencer A, Buck M, Boyd J, Dobson CM, Redfield C, Smith LJ (2001) A refined solution structure of hen lysozyme determined using residual dipolar coupling data. Protein Sci 10:677–688

    Article  PubMed  CAS  Google Scholar 

  • Steinmetz MO, Jelesarov I, Matousek WM, Honnappa S, Jahnke W, Missimer JH, Frank S, Alexandrescu AT, Kammerer RA (2007) Molecular basis of coiled-coil formation. PNAS 17:7062–7067

    Article  Google Scholar 

  • van Gunsteren WF, Billeter SR, Eising AA, Hünenberger PH, Krüger P, Mark AE, Scott WRP, Tironi IG (1996) Biomolecular simulation: the GROMOS96 manual and user guide. Hochschulverlag AG, ETH Zurich

  • Weiner PK, Kollman PA (1981) Amber—assisted model-building with energy refinement—a general program for modeling molecules and their interactions. J Comput Chem 2:287–303

    Article  CAS  Google Scholar 

  • Wüthrich K, Billeter M, Braun W (1983) Pseudo-structures for the 20 common amino acids for use in studies of protein conformations by measurements of intramolecular proton-proton distance constraints with nuclear magnetic resonance. J Mol Biol 169:949–61

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Hao Fan, Philippe Hünenberger, Zuo Le, Haiyan Liu, Alpesh Malde, Chris Oostenbrink, Xavier Perole, David Poger, Maria Reif, Denise Steiner, Xue Ying and Bojan Zagrovic for stimulating discussions and contributions to the force field modifications. This work was financially supported by the National Center of Competence in Research (NCCR) in Structural Biology and by grant number 200020-121913 of the Swiss National Science Foundation, by grant number 228076 of the European Research Council and by grant number DP0770375 of the Australian Research Council. All funding is gratefully acknowledged.

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Authors and Affiliations

  1. Laboratory of Physical Chemistry, Swiss Federal Institute of Technology ETH, 8093, Zürich, Switzerland

    Nathan Schmid, Andreas P. Eichenberger, Alexandra Choutko, Sereina Riniker & Wilfred F. van Gunsteren

  2. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia

    Moritz Winger & Alan E. Mark

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  1. Nathan Schmid
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  2. Andreas P. Eichenberger
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  3. Alexandra Choutko
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  4. Sereina Riniker
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  6. Alan E. Mark
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  7. Wilfred F. van Gunsteren
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Correspondence to Wilfred F. van Gunsteren.

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Schmid, N., Eichenberger, A.P., Choutko, A. et al. Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur Biophys J 40, 843–856 (2011). https://doi.org/10.1007/s00249-011-0700-9

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