A Modified Version of the Cornell et al.Force Field with Improved Sugar Pucker Phases and Helical Repeat

Abstract

We have examined some subtle parameter modifications to the Cornell et al. force field, which has proven quite successful in reproducing nucleic acid properties, but whose C2'-endo sugar pucker phase and helical repeat for B DNA appear to be somewhat underestimated. Encouragingly, the addition of a single V2 term involving the atoms C(sp3)-O-(sp3)-C(sp3)-N(sp2), which can be nicely rationalized because of the anomeric effect (lone pairs on oxygen are preferentially oriented relative to the electron withdrawing N), brings the sugar pucker phase of C2'-endo sugars to near perfect agreement with ab initio calculations (W near 162 degrees). Secondly, the use of high level ab initio calculations on entire nucleosides (in contrast to smaller model systems necessitated in 1994-95 by computer limitations) lets one improve the chi torsional potential for nucleic acids. Finally, the O(sp3)-C(sp3)- C(sp3)-O(sp3) V2 torsional potential has been empirically adjusted to reproduce the ab initio calculated relative energy of C2'-endo and C3'-endo nucleosides. These modifications are tested in molecular dynamics simulations of mononucleosides (to assess sugar pucker percentages) and double helices of DNA and RNA (to assess helical and sequence specific structural properties). In both areas, the modified force field leads to improved agreement with experimental data.