Modern Computtional Studies of Interactions of Nucleic acid bases, their influence on the structure and dynamics of nucleic acids
Interactions of nucleic acid bases significantly influence the structure, stability and dynamics of nucleic acids. Recent advances of computer hardware and software allowed very significant improvements of our understanding of these interactions. Modern ab initio quantum chemical approaches with inclusion of electron correlation effects are for base - base interactions more accurate than any currently available gas phase physico-chemical experiment. These calculations for example identified the nature of aromatic base stacking and ruled out several older theories of stacking popular in biological literature (such as the out-of-plane p-p and induction models of stacking). In absence of relevant experiments, ab initio calculations furnish a major portion of reference data for verification and parametrization of empirical force fields for biomolecular modeling. Ab initio calculations also allow to study effects that are not included in present force fields, such as amino group pyramidalization, polarization effects, cation binding to nucleobases, and others. Great improvements have also been achieved in developments of classical molecular dynamics tecnhiques, mainly due to the advance of accurate methods for long range electrostatic interactions and new force fields. Though the accuracy of the MD approach is obviously limited by the nanosecond time scale of simulations and the quality of force fields this method is capable to provide very valuable qualitative results, when applied properly. Base pairing and stacking interactions appear to be well approximated by the recently released force fields.
P. Hobza, J. Sponer, Chem. Rev. 99, 3247 (1999)
J. Sponer and P. Hobza
J. Heyrovsky Institute of Physical Chemistry,