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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

Lowest energy structuresobtained from simulated annealing procedurewith the NN model with some of bonded potentials switched off. (a)Dihedral angle potentials S5–P5–S–P3, P5–S–P3–S3,S5–P5–S–B, and P3–S3–S–Bswitched off. (b) Additionally, rotamer-like potentials P5–S–B,P3–S–B, and P5–P3–S–B switchedoff.
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fig14: Lowest energy structuresobtained from simulated annealing procedurewith the NN model with some of bonded potentials switched off. (a)Dihedral angle potentials S5–P5–S–P3, P5–S–P3–S3,S5–P5–S–B, and P3–S3–S–Bswitched off. (b) Additionally, rotamer-like potentials P5–S–B,P3–S–B, and P5–P3–S–B switchedoff.

Mentions: In our recent paper, it was shown that dihedralangle bonded potentials are not prerequisites for double-helix formation,which is rather driven by base–base dipole interaction.43 Also, the model developed by Ouldridge et al.does not require backbone dihedral angle potentials to obtain DNAduplex hybridization.36 A question can,therefore, be asked: Are the backbone potentials a necessary factorfor double-helix formation, or is this process solely dependent onthe base stacking and pairing? The problem was addressed by runningthe simulated annealing procedure with P5–S–P3–S3,S5–P5–S–P3, S5–P5–S–B, andS3–P3–S–B dihedral angle potentials switchedoff. The test performed on the Drew–Dickerson dodecamer showedthe same efficiency of double-helix hybridization process (24%). Thelowest energy structure shown in Figure 14ais only 3.2 Å away from the experimental structure. Next, improperrotamer-like potentials P5–P3–B–S, P5–S–B,and P3–S–B were additionally switched off. The lowestenergy structures have a ladder-like shape, as shown in Figure 14b. It seems that backbone dihedral angle potentialsare not really necessary for DNA duplex hybridization. Switching offrotamer-like potentials (P5–S–B, P3–S–B,and P5–P3–S–B) causes formation of ladder-likestructures instead of double-helices. This effect might be relatedto the lack of specificity of base–base interactions, whichmight be the result of overestimation of base–base van derWaals interactions with respect to dipole–dipole electrostaticinteractions. Nevertheless, the dipolar-bead model suggests that onlybackbone bond-stretching, angle-bending, and rotamer-like potentialsare necessary for double stranded DNA hybridization.


DNA Duplex Formation with a Coarse-Grained Model.

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

Lowest energy structuresobtained from simulated annealing procedurewith the NN model with some of bonded potentials switched off. (a)Dihedral angle potentials S5–P5–S–P3, P5–S–P3–S3,S5–P5–S–B, and P3–S3–S–Bswitched off. (b) Additionally, rotamer-like potentials P5–S–B,P3–S–B, and P5–P3–S–B switchedoff.
© Copyright Policy
Related In: Results  -  Collection

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

fig14: Lowest energy structuresobtained from simulated annealing procedurewith the NN model with some of bonded potentials switched off. (a)Dihedral angle potentials S5–P5–S–P3, P5–S–P3–S3,S5–P5–S–B, and P3–S3–S–Bswitched off. (b) Additionally, rotamer-like potentials P5–S–B,P3–S–B, and P5–P3–S–B switchedoff.
Mentions: In our recent paper, it was shown that dihedralangle bonded potentials are not prerequisites for double-helix formation,which is rather driven by base–base dipole interaction.43 Also, the model developed by Ouldridge et al.does not require backbone dihedral angle potentials to obtain DNAduplex hybridization.36 A question can,therefore, be asked: Are the backbone potentials a necessary factorfor double-helix formation, or is this process solely dependent onthe base stacking and pairing? The problem was addressed by runningthe simulated annealing procedure with P5–S–P3–S3,S5–P5–S–P3, S5–P5–S–B, andS3–P3–S–B dihedral angle potentials switchedoff. The test performed on the Drew–Dickerson dodecamer showedthe same efficiency of double-helix hybridization process (24%). Thelowest energy structure shown in Figure 14ais only 3.2 Å away from the experimental structure. Next, improperrotamer-like potentials P5–P3–B–S, P5–S–B,and P3–S–B were additionally switched off. The lowestenergy structures have a ladder-like shape, as shown in Figure 14b. It seems that backbone dihedral angle potentialsare not really necessary for DNA duplex hybridization. Switching offrotamer-like potentials (P5–S–B, P3–S–B,and P5–P3–S–B) causes formation of ladder-likestructures instead of double-helices. This effect might be relatedto the lack of specificity of base–base interactions, whichmight be the result of overestimation of base–base van derWaals interactions with respect to dipole–dipole electrostaticinteractions. Nevertheless, the dipolar-bead model suggests that onlybackbone bond-stretching, angle-bending, and rotamer-like potentialsare necessary for double stranded DNA hybridization.

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