Rapid communication capturing the destabilizing effect of dihydrouridine through molecular simulations

The structural effects of the commonly occurring modified nucleoside dihydrouridine (D) observed experimentally in model oligonucleotides include a strong destabilization of the C3'-endo sugar conformation of D, the disruption of stacking interactions of neighboring residues with D and a possible destabilization of the C3'-endo sugar pucker of the 5'-neighboring nucleoside. Our simulations with a combination of a set of parameters for modified RNA residues with the recently developed AMBER FF99χ force field having reoptimized glycosidic torsion angle parameters for standard nucleosides was found to reproduce the destabilizing effect of dihydrouridine better than with the AMBER FF99 force field for nucleic acids for which the parameters for the modified residues were originally developed.