Abstract
Molecular dynamics (MD) simulations at the atomic scale are a powerful tool to study the structure and dynamics of model biological systems. However, because of their high computational cost, the time and length scales of atomistic simulations are limited. Biologically important processes, such as protein folding, ion channel gating, signal transduction, and membrane remodeling, are difficult to investigate using atomistic simulations. Coarse-graining reduces the computational cost of calculations by reducing the number of degrees of freedom in the model, allowing simulations of larger systems for longer times. In the first part of this chapter we review briefly some of the coarse-grained models available for proteins, focusing on the specific scope of each model. Then we describe in more detail the MARTINI coarse-grained force field, and we illustrate how to set up and run a simulation of a membrane protein using the Gromacs software package. We explain step-by-step the preparation of the protein and the membrane, the insertion of the protein in the membrane, the equilibration of the system, the simulation itself, and the analysis of the trajectory.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Dror RO, Dirks RM, Grossman JP, Xu H, Shaw DE (2012) Biomolecular simulation: a computational microscope for molecular biology. Annu Rev Biophys 41:429–452
Shaw DE, Chao JC, Eastwood MP, Gagliardo J, Grossman JP, Ho CR et al (2008) Anton, a special-purpose machine for molecular dynamics simulation. Commun ACM 51:91
Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) How fast-folding proteins fold. Science 334:517–520
Bussi G, Laio A, Parrinello M (2006) Equilibrium free energies from non-equilibrium metadynamics. Phys Rev Lett 96:090601
Sugita Y, Okamoto Y (1999) Replica-exchange molecular dynamics method for protein folding. Chem Phys Lett 314:141–151
Torrie GM, Valleau JP (1977) Nonphysical sampling distributions in Monte Carlo free-energy estimation: umbrella sampling. J Comput Phys 23:187–199
Carbone P, Varzaneh HAK, Chen X, Müller-Plathe F (2008) Transferability of coarse-grained force fields: the polymer case. J Chem Phys 128:064904
Levitt M, Warshel A (1975) Computer simulation of protein folding. Nature 253:694–698
Liwo A, Oldziej S, Pincus MR, Wawak RJ, Rackovsky S, Scheraga HA (1997) A united-residue force field for off-lattice protein-structure simulations. I. Functional forms and parameters of long-range side-chain interaction potentials from protein crystal data. J Comput Chem 18:849–873
Maupetit J, Tuffery P, Derreumaux P (2007) A coarse-grained protein force field for folding and structure prediction. Proteins 69:394–408
Bereau T, Deserno M (2009) Generic coarse-grained model for protein folding and aggregation. J Chem Phys 130:235106
Pasi M, Lavery R, Ceres N (2013) PaLaCe: a coarse-grain protein model for studying mechanical properties. J Chem Theory Comput 9:785–793
Zacharias M (2003) Protein-protein docking with a reduced protein model accounting for side-chain flexibility. Protein Sci 12:1271–1282
Setny P, Zacharias M (2011) A coarse-grained force field for Protein-RNA docking. Nucleic Acids Res 39:9118–9129
Den Otter WK, Renes MR, Briels WJ (2010) Asymmetry as the key to clathrin cage assembly. Biophys J 99:1231–1238
Matthews R, Likos CN (2013) Structures and pathways for clathrin self-assembly in the bulk and on membranes. Soft Matter 9:5794–5806. doi:10.1039/c3sm50737h
Shi Q, Izvekov S, Voth GA (2006) Mixed atomistic and coarse-grained molecular dynamics: simulation of a membrane-bound ion channel. J Phys Chem B 110:15045–15048
Rzepiela AJ, Louhivuori M, Peter C, Marrink SJ (2011) Hybrid simulations: combining atomistic and coarse-grained force fields using virtual sites. Phys Chem Chem Phys 13:10437–10448
Zacharias M (2013) Combining coarse-grained nonbonded and atomistic bonded interactions for protein modeling. Proteins 81:81–92
Taylor WR, Katsimitsoulia Z (2010) A coarse-grained molecular model for actin-myosin simulation. J Mol Graph Model 29:266–279
Praprotnik M, Delle Site L (2013) Multiscale molecular modeling. Methods Mol Biol 924:567–583
Marrink SJ, de Vries AH, Mark AE (2004) Coarse grained model for semiquantitative lipid simulations. J Phys Chem B 108:750–760
Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, De Vries AH (2007) The MARTINI force field: coarse grained model for biomolecular simulations. J Phys Chem B 111:7812–7824
Monticelli L, Kandasamy SK, Periole X, Larson RG, Tieleman DP, Marrink S-J (2008) The MARTINI coarse-grained force field: extension to proteins. J Chem Theory Comput 4:819–834
De Jong DH, Singh G, Bennett WFD, Arnarez C, Wassenaar TA, Schäfer LV et al (2013) Improved parameters for the martini coarse-grained protein force field. J Chem Theory Comput 9:687–697
Marrink SJ, Tieleman DP (2013) Perspective on the Martini model. Chem Soc Rev 42:6801–6822. doi:10.1039/c3cs60093a
López CA, Rzepiela AJ, de Vries AH, Dijkhuizen L, Hünenberger PH, Marrink SJ (2009) Martini coarse-grained force field: extension to carbohydrates. J Chem Theory Comput 5:3195–3210
Rossi G, Fuchs PFJ, Barnoud J, Monticelli L (2012) A coarse-grained MARTINI model of polyethylene glycol and of polyoxyethylene alkyl ether surfactants. J Phys Chem B 116:14353–14362
Rossi G, Monticelli L, Puisto SR, Vattulainen I, Ala-Nissila T (2011) Coarse-graining polymers with the MARTINI force-field: polystyrene as a benchmark case. Soft Matter 7:698
Wong-Ekkabut J, Baoukina S, Triampo W, Tang I-M, Tieleman DP, Monticelli L (2008) Computer simulation study of fullerene translocation through lipid membranes. Nat Nanotechnol 3:363–368
Monticelli L (2012) On atomistic and coarse-grained models for C60 fullerene. J Chem Theory Comput 8:1370–1378
Marrink SJ, Mark AE (2003) The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J Am Chem Soc 125:11144–11145
Risselada HJ, Marrink SJ (2008) The molecular face of lipid rafts in model membranes. Proc Natl Acad Sci U S A 105:17367–17372
Baoukina S, Marrink SJ, Tieleman DP (2012) Molecular structure of membrane tethers. Biophys J 102:1866–1871
Baron R, Trzesniak D, de Vries AH, Elsener A, Marrink SJ, van Gunsteren WF (2007) Comparison of thermodynamic properties of coarse-grained and atomic-level simulation models. ChemPhysChem 8:452–461
Shih AY, Arkhipov A, Freddolino PL, Schulten K (2006) Coarse grained protein-lipid model with application to lipoprotein particles. J Phys Chem B 110:3674–3684
Shinoda W, DeVane R, Klein ML (2010) Zwitterionic lipid assemblies: molecular dynamics studies of monolayers, bilayers, and vesicles using a new coarse grain force field. J Phys Chem B 114:6836–6849
Yesylevskyy SO, Schäfer LV, Sengupta D, Marrink SJ (2010) Polarizable water model for the coarse-grained MARTINI force field. PLoS Comput Biol 6:e1000810
Monticelli L, Tieleman DP, Fuchs PFJ (2010) Interpretation of 2H-NMR experiments on the orientation of the transmembrane helix WALP23 by computer simulations. Biophys J 99:1455–1464
Castillo N, Monticelli L, Barnoud J, Tieleman DP (2013) Free energy of WALP23 dimer association in DMPC, DPPC, and DOPC bilayers. Chem Phys Lipids 169:95–105
Deplazes E, Louhivuori M, Jayatilaka D, Marrink SJ, Corry B (2012) Structural Investigation of MscL gating using experimental data and coarse grained MD simulations. PLoS Comput Biol 8:e1002683
Periole X, Cavalli M, Marrink S-J, Ceruso MA (2009) Combining an elastic network with a coarse-grained molecular force field: structure, dynamics, and intermolecular recognition. J Chem Theory Comput 5:2531–2543
Dony N, Crowet JM, Joris B, Brasseur R, Lins L (2013) SAHBNET, an accessible surface-based elastic network: an application to membrane protein. Int J Mol Sci 14:11510–11526
Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R et al (2013) GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29:845–854
Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637
Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, Shichida Y (2002) Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc Natl Acad Sci U S A 99:5982–5987
Humphrey W, Dalke A, Schulten K (1996) VMD – visual molecular dynamics. J Mol Graph 14:33–38
Jo S, Lim JB, Klauda JB, Im W (2009) CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes. Biophys J 97:50–58
Lomize MA, Lomize AL, Pogozheva ID, Mosberg HI (2006) OPM: orientations of proteins in membranes database. Bioinformatics 22:623–625
Lomize MA, Pogozheva ID, Joo H, Mosberg HI, Lomize AL (2012) OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res 40:D370–D376
Tusnády GE, Dosztányi Z, Simon I (2004) Transmembrane proteins in the Protein Data Bank: identification and classification. Bioinformatics 20:2964–2972
Tusnády GE, Dosztányi Z, Simon I (2005) PDB_TM: selection and membrane localization of transmembrane proteins in the protein data bank. Nucleic Acids Res 33:D275–D278
Kozma D, Simon I, Tusnády GE (2013) PDBTM: protein data bank of transmembrane proteins after 8 years. Nucleic Acids Res 41:D524–D529
Tusnády GE, Dosztányi Z, Simon I (2005) TMDET: web server for detecting transmembrane regions of proteins by using their 3D coordinates. Bioinformatics 21:1276–1277
Schmidt TH, Kandt C (2012) LAMBADA and InflateGRO2: efficient membrane alignment and insertion of membrane proteins for molecular dynamics simulations. J Chem Inf Model 52:2657–2669
Wolf MG, Hoefling M, Aponte-Santamaría C, Grubmüller H, Groenhof G (2010) g_membed: efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation. J Comput Chem 31:2169–2174
Kandt C, Ash WL, Tieleman DP (2007) Setting up and running molecular dynamics simulations of membrane proteins. Methods 41:475–488
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
Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126:014101
Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52:7182
Acknowledgments
The authors thank Juliette Martin and Nicoletta Ceres for their useful comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Barnoud, J., Monticelli, L. (2015). Coarse-Grained Force Fields for Molecular Simulations. In: Kukol, A. (eds) Molecular Modeling of Proteins. Methods in Molecular Biology, vol 1215. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1465-4_7
Download citation
DOI: https://doi.org/10.1007/978-1-4939-1465-4_7
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-1464-7
Online ISBN: 978-1-4939-1465-4
eBook Packages: Springer Protocols