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Ab Initio Quantum Mechanical Study of the Structures and Energies for the Pseudorotation of 5‘-Dehydroxy Analogues of 2‘-Deoxyribose and Ribose Sugars
journal contribution
posted on 1999-01-26, 00:00 authored by Ken A. Brameld, William A. GoddardWe have used ab initio quantum mechanical (QM) methods to determine the potential energy of
pseudorotation for 3,4-dihydroxy-5-methyl-2-(1-pyrollyl)tetrahydrofuran and 4-hydroxy-5-methyl-2-(1-pyrollyl)tetrahydrofuran, close analogues of 2‘-deoxyribose and ribose sugars. The pyrrole is a substitute for the naturally
occurring nucleic acid bases: adenine, thymine, guanine, cytosine, and uracil. At the highest calculation level
(LMP2/cc-pVTZ(-f)//HF/6-31G**) for 2‘-deoxyribose, we find the C2‘-endo conformation is the global
minimum. The C3‘-endo conformation is a local minimum 0.6 kcal/mol higher in energy, and an eastern
barrier of 1.6 kcal/mol separates the two minima. Pseudorotation energies of ribose are quite complex and are
strongly affected by local orientations of the 2‘ and 3‘ hydroxyl groups. When the hydroxyl groups are allowed
to assume any conformation, the global minimum remains the C2‘-endo conformation. The eastern barrier
increases slightly to 1.8 kcal/mol, and the C3‘-endo local minimum lies 0.6 kcal/mol above the global minimum.
Constraining the torsion angle of the C3‘ hydroxyl group to −146°, as is found in RNA polymers, results in
the C3‘-endo conformation becoming the only energy minimum with a C2‘-endo conformation 1.9 kcal/mol
higher in energy. Bond angles within the pentofuranose ring are correlated to the pseudorotational phase, as
is observed by X-ray crystallography and is predicted by pseudorotation theory. Finally, a force field for use
in molecular mechanics and dynamics simulations is presented which reproduces the QM potential energies
for the 2‘-deoxyribose and ribose sugars.