QM calculations were performed using the program Gaussian0340 to obtain an estimate of the potential
energy associated with rotation of the 2′-hydroxyl moiety. The RNA
backbone dihedrals (α: P-O5′, β:
O5′-C5′, γ: C5′-C4′, δ:
C4′-C3′, ε: C3′-O3′, and ζ:
O3′-P) or the RNA glycosidic linkage dihedral (χ:
C1′-N1/N9) were fixed while dihedral potential energy scans were
performed for the 2′-hydroxyl as previously described 41 (link). Scans were performed at the MP2/6-31+G(d)
level of theory followed by single point calculations at the RIMP2/cc-pVTZ level
performed using the Q-Chem program 42 (link).
This level of theory has previously been shown to be sufficiently accurate for a
number of systems.25 ,43 (link) For this study, the 2′-hydroxyl dihedral
angle is defined with the respect to
C1′-C2′-O2′-H2′ (note that the atom names are
representative of those in the CHARMM27 all-atom additive nucleic acid force
field). The dihedral was scanned at 15° intervals from 0° to
360° for each of the compounds. Analogous potential-energy scans were
performed using the original CHARMM27 all-atom additive force field and several
trial revisions of the force field developed in the present study. Empirical
scans were performed using the same constraints as in the QM scans, implemented
as a harmonic potential with force constant 10,000 kcal/mol/rad2 (link) on the respective backbone and glycosidic linkage
dihedrals, with the remaining degrees of freedom optimized using the
Newton-Raphson algorithm to a final root-means-square (RMS) gradient of
10−6 kcal/mol/Å. All nonbonded interactions were
included in the calculations.
energy associated with rotation of the 2′-hydroxyl moiety. The RNA
backbone dihedrals (α: P-O5′, β:
O5′-C5′, γ: C5′-C4′, δ:
C4′-C3′, ε: C3′-O3′, and ζ:
O3′-P) or the RNA glycosidic linkage dihedral (χ:
C1′-N1/N9) were fixed while dihedral potential energy scans were
performed for the 2′-hydroxyl as previously described 41 (link). Scans were performed at the MP2/6-31+G(d)
level of theory followed by single point calculations at the RIMP2/cc-pVTZ level
performed using the Q-Chem program 42 (link).
This level of theory has previously been shown to be sufficiently accurate for a
number of systems.25 ,43 (link) For this study, the 2′-hydroxyl dihedral
angle is defined with the respect to
C1′-C2′-O2′-H2′ (note that the atom names are
representative of those in the CHARMM27 all-atom additive nucleic acid force
field). The dihedral was scanned at 15° intervals from 0° to
360° for each of the compounds. Analogous potential-energy scans were
performed using the original CHARMM27 all-atom additive force field and several
trial revisions of the force field developed in the present study. Empirical
scans were performed using the same constraints as in the QM scans, implemented
as a harmonic potential with force constant 10,000 kcal/mol/rad2 (link) on the respective backbone and glycosidic linkage
dihedrals, with the remaining degrees of freedom optimized using the
Newton-Raphson algorithm to a final root-means-square (RMS) gradient of
10−6 kcal/mol/Å. All nonbonded interactions were
included in the calculations.
