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DNA Duplex Formation with a Coarse-Grained Model.

Maciejczyk M, Spasic A, Liwo A, Scheraga HA - J Chem Theory Comput (2014)

Bottom Line: Chem. 2010, 31, 1644].Interactions with the solvent and an ionic cloud are approximated by a multipole-multipole Debye-Hückel model.It is the first coarse-grained model, in which both bonded and nonbonded interactions were parametrized ab initio and which folds stable double helices from separated complementary strands, with the final conformation close to the geometry of experimentally determined structures.

View Article: PubMed Central - PubMed

Affiliation: Baker Laboratory of Chemistry, Cornell University , Ithaca, New York 14850, United States ; Department of Physics and Biophysics, Faculty of Food Sciences, University of Warmia and Mazury , 11-041 Olsztyn, Poland.

ABSTRACT
A middle-resolution coarse-grained model of DNA is proposed. The DNA chain is built of spherical and planar rigid bodies connected by elastic virtual bonds. The bonded part of the potential energy function is fit to potentials of mean force of model systems. The rigid bodies are sets of neutral, charged, and dipolar beads. Electrostatic and van der Waals interactions are parametrized by our recently developed procedure [Maciejczyk, M.; Spasic, A.; Liwo, A.; Scheraga, H.A. J. Comp. Chem. 2010, 31, 1644]. Interactions with the solvent and an ionic cloud are approximated by a multipole-multipole Debye-Hückel model. A very efficient R-RATTLE algorithm, for integrating the movement of rigid bodies, is implemented. It is the first coarse-grained model, in which both bonded and nonbonded interactions were parametrized ab initio and which folds stable double helices from separated complementary strands, with the final conformation close to the geometry of experimentally determined structures.

No MeSH data available.


Related in: MedlinePlus

Energy vs RMSD with respect to the experimental structurefor the 1BNA dodecamer. Two majorclusters, corresponding to antiparallel and parallel dsDNA, and theenergy-minimized experimental structure are pointed by arrows.
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fig7: Energy vs RMSD with respect to the experimental structurefor the 1BNA dodecamer. Two majorclusters, corresponding to antiparallel and parallel dsDNA, and theenergy-minimized experimental structure are pointed by arrows.

Mentions: Nevertheless 24% of extendedtrajectories led to double-helicalstructure with more than 10 native contacts for 1BNA molecule. Roughlythe same number of structures broke up into separate chains or formedmisfolded structures without native contacts. 41% trajectories endedup in misfolded structures with 1–3 native contacts, whichwere mostly parallel dsDNA’s, in which 5′-end of onechain makes nonative contacts with 5′-end of the other chain.Figure 7 shows the potential energy of finalstructures as a function of all-bead RMSD computed with respect toexperimental structure. Two low-energy clusters of structures areclearly visible. The one located in the lower left corner of Figure 7 is a cluster of correctly folded antiparallel dsDNA’sand the other one represents misfolded parallel dsDNA’s, inwhich 3′-ends (and 5′-ends) of chains are paired. Theimportant observation that comes from this graph is that lowest energystructure is clearly located in the correctly folded group and itsenergy is around 10 kcal/mol lower than misfolded parallel dsDNA,although the lowest energy structure is not the structure with lowestRMSD. The mean potential energy of antiparallel dsDNA cluster is around8 kcal/mol lower than the mean energy of the parallel DNA cluster,which clearly favors correctly folded structures, although this differencefor real systems might be larger (experimental structures of the parallelDrew–Dickerson dodecamer were not observed) and further refinementof the electrostatics and/or Lennard-Jones balance of the model isrequired to increase this gap and improve specificity of base–baseinteractions.


DNA Duplex Formation with a Coarse-Grained Model.

Maciejczyk M, Spasic A, Liwo A, Scheraga HA - J Chem Theory Comput (2014)

Energy vs RMSD with respect to the experimental structurefor the 1BNA dodecamer. Two majorclusters, corresponding to antiparallel and parallel dsDNA, and theenergy-minimized experimental structure are pointed by arrows.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230386&req=5

fig7: Energy vs RMSD with respect to the experimental structurefor the 1BNA dodecamer. Two majorclusters, corresponding to antiparallel and parallel dsDNA, and theenergy-minimized experimental structure are pointed by arrows.
Mentions: Nevertheless 24% of extendedtrajectories led to double-helicalstructure with more than 10 native contacts for 1BNA molecule. Roughlythe same number of structures broke up into separate chains or formedmisfolded structures without native contacts. 41% trajectories endedup in misfolded structures with 1–3 native contacts, whichwere mostly parallel dsDNA’s, in which 5′-end of onechain makes nonative contacts with 5′-end of the other chain.Figure 7 shows the potential energy of finalstructures as a function of all-bead RMSD computed with respect toexperimental structure. Two low-energy clusters of structures areclearly visible. The one located in the lower left corner of Figure 7 is a cluster of correctly folded antiparallel dsDNA’sand the other one represents misfolded parallel dsDNA’s, inwhich 3′-ends (and 5′-ends) of chains are paired. Theimportant observation that comes from this graph is that lowest energystructure is clearly located in the correctly folded group and itsenergy is around 10 kcal/mol lower than misfolded parallel dsDNA,although the lowest energy structure is not the structure with lowestRMSD. The mean potential energy of antiparallel dsDNA cluster is around8 kcal/mol lower than the mean energy of the parallel DNA cluster,which clearly favors correctly folded structures, although this differencefor real systems might be larger (experimental structures of the parallelDrew–Dickerson dodecamer were not observed) and further refinementof the electrostatics and/or Lennard-Jones balance of the model isrequired to increase this gap and improve specificity of base–baseinteractions.

Bottom Line: Chem. 2010, 31, 1644].Interactions with the solvent and an ionic cloud are approximated by a multipole-multipole Debye-Hückel model.It is the first coarse-grained model, in which both bonded and nonbonded interactions were parametrized ab initio and which folds stable double helices from separated complementary strands, with the final conformation close to the geometry of experimentally determined structures.

View Article: PubMed Central - PubMed

Affiliation: Baker Laboratory of Chemistry, Cornell University , Ithaca, New York 14850, United States ; Department of Physics and Biophysics, Faculty of Food Sciences, University of Warmia and Mazury , 11-041 Olsztyn, Poland.

ABSTRACT
A middle-resolution coarse-grained model of DNA is proposed. The DNA chain is built of spherical and planar rigid bodies connected by elastic virtual bonds. The bonded part of the potential energy function is fit to potentials of mean force of model systems. The rigid bodies are sets of neutral, charged, and dipolar beads. Electrostatic and van der Waals interactions are parametrized by our recently developed procedure [Maciejczyk, M.; Spasic, A.; Liwo, A.; Scheraga, H.A. J. Comp. Chem. 2010, 31, 1644]. Interactions with the solvent and an ionic cloud are approximated by a multipole-multipole Debye-Hückel model. A very efficient R-RATTLE algorithm, for integrating the movement of rigid bodies, is implemented. It is the first coarse-grained model, in which both bonded and nonbonded interactions were parametrized ab initio and which folds stable double helices from separated complementary strands, with the final conformation close to the geometry of experimentally determined structures.

No MeSH data available.


Related in: MedlinePlus