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. 2011 Sep 13;7(9):2886-2902.
doi: 10.1021/ct200162x. Epub 2011 Aug 2.

Refinement of the Cornell et al. Nucleic Acids Force Field Based on Reference Quantum Chemical Calculations of Glycosidic Torsion Profiles

Marie Zgarbová, Michal Otyepka, Jiří Sponer, Arnošt Mládek, Pavel Banáš, Thomas E Cheatham 3rd, Petr Jurečka
Free PMC article

Refinement of the Cornell et al. Nucleic Acids Force Field Based on Reference Quantum Chemical Calculations of Glycosidic Torsion Profiles

Marie Zgarbová et al. J Chem Theory Comput. .
Free PMC article

Abstract

We report a reparameterization of the glycosidic torsion χ of the Cornell et al. AMBER force field for RNA, χ(OL). The parameters remove destabilization of the anti region found in the ff99 force field and thus prevent formation of spurious ladder-like structural distortions in RNA simulations. They also improve the description of the syn region and the syn-anti balance as well as enhance MD simulations of various RNA structures. Although χ(OL) can be combined with both ff99 and ff99bsc0, we recommend the latter. We do not recommend using χ(OL) for B-DNA because it does not improve upon ff99bsc0 for canonical structures. However, it might be useful in simulations of DNA molecules containing syn nucleotides. Our parametrization is based on high-level QM calculations and differs from conventional parametrization approaches in that it incorporates some previously neglected solvation-related effects (which appear to be essential for obtaining correct anti/high-anti balance). Our χ(OL) force field is compared with several previous glycosidic torsion parametrizations.

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Figures

Figure 1
Figure 1
Chemical structures and atom-naming conventions for the model ribonucleosides used in our derivation of χ torsion parameters for cytosine (C), adenine (A), guanine (G), and uracil (U). The dihedral angle χ is defined by the O4′–C1′–N1–C2 atoms for C and U and by the O4′–C1′–N9–C4 atoms for A and G (this definition is used throughout this work). Note, however, that in ff94, ff98, and ff99 force fields the χ parameters are actually assigned to the complementary angle, specifically O4′–C1′–N1–C6 for C and U and O4′–C1′–N9–C8 for A and G.
Figure 2
Figure 2
Torsion profiles for guanine nucleoside (dG) calculated at various levels of theory in vacuo. The reference method is CBS(T). (Top) Profiles obtained with the wave function methods: CBS(T) (black), HF/6-31G* (green), MP2/6-31G* (blue), and MP2/CBS (red). (Bottom) Profiles obtained with the DFT methods: DFT-D (PBE/6-311++G(3df,3pd)/1.06-23) (orange), M06 (red), M06-2X (blue), and the reference CBS(T) profile (black). Energies are offset to the anti minimum structure.
Figure 3
Figure 3
Torsion profiles for cytosine calculated in vacuo (left), with COSMO continuum solvent (middle), and the χ dihedral term’s contribution to the torsion derived from the continuum solvent data (right) of the cytosine 2-deoxyribonucleoside with C2′-endo and C3′-endo sugar puckers and the ribonucleoside with C3′-endo sugar pucker (full, dotted, and dashed lines, respectively).
Figure 4
Figure 4
(Top) Torsion profiles for dC calculated as QM energy based on QM-optimized geometry (EQM//QM,COSMO, full line), MM–χ energy based on MM-optimized geometry (E–χMM//MM,PB, dashed line), and MM–χ energy based on QM-optimized geometry (E–χMM//QM,PB, dotted line). (Bottom) χ dihedral terms Edih,χsolv derived from EQM//QM,COSMO – E–χMM//MM,PB (QM//QM-MM//MM, dashed line) and EQM//QM,COSMO – E–χMM//QM,PB (QM//QM-MM//QM, dotted line) normalized to χ = 250°. The ff99bsc0 force field was used in all cases, and energies are in kcal/mol.
Figure 5
Figure 5
χ torsion profiles for dG (full line) and rG (dashed line), indicating typical average X-ray values for A-RNA, B-DNA, and Z-DNA. PBE/LP data including solvent effects.
Figure 6
Figure 6
Torsion profiles for the χ angle (on the left, ff99-optimized geometries) and the χ dihedral terms (on the right) of ff99 (black), Ode et al. (blue), Yildirim et al. (green), and parameters derived herein (χOL-DFT orange, χOL red) for ribonucleosides. The dihedral term was offset to χ = 250°, and idealized geometries were used to calculate the χ dihedral terms on the right to facilitate comparison with published data (see also text).
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