Refinement of the Sugar Puckering Torsion Potential in the AMBER DNA Force Field

The transition from B-DNA to A-DNA occurs in many protein–DNA
interactions or in DNA/RNA hybrid duplexes, and thus plays a role
in many important biomolecular processes that convey the biological
function of DNA. However, the stability of A-DNA is severely underestimated
in current AMBER force fields such as OL15, OL21 or bsc1, potentially
leading to unstable or deformed protein–DNA complexes. In this
study, we refine the deoxyribose dihedral potential to increase the
stability of the north (N) puckering present in A-DNA. The new parameters,
termed OL24, model A/B equilibrium in B-DNA duplexes in water in good
agreement with nuclear magnetic resonance (NMR) experiment. They also
improve the description of DNA/RNA hybrids and the transition of the
DNA duplex to the A-form in concentrated ethanol solutions. These
refinements significantly improve the modeling of protein–DNA
complexes, increasing their structural stability and A-form population,
while maintaining accurate representation of canonical B-DNA duplexes.
Overall, the new parameters should allow more reliable modeling of
the thermodynamic equilibrium between A- and B-DNA forms and the interactions
of DNA with proteins.