A measure of bending in nucleic acids structures applied to A-tract DNA

A method is proposed to measure global bending in DNA and RNA structures. It relies on a properly defined averaging of base-fixed coordinate frames, computes mean frames of suitably chosen groups of bases and uses these mean frames to evaluate bending. The method is applied to DNA A-tracts, known to induce considerable bend to the double helix. We performed atomistic molecular dynamics simulations of sequences containing the A4T4 and T4A4 tracts, in a single copy and in two copies phased with the helical repeat. Various temperature and salt conditions were investigated. Our simulations indicate bending by roughly 10° per A4T4 tract into the minor groove, and an essentially straight structure containing T4A4, in agreement with electrophoretic mobility data. In contrast, we show that the published NMR structures of analogous sequences containing A4T4 and T4A4 tracts are significantly bent into the minor groove for both sequences, although bending is less pronounced for the T4A4 containing sequence. The bending magnitudes obtained by frame averaging are confirmed by the analysis of superhelices composed of repeated tract monomers

Comparison of ab Initio, DFT, and Semiempirical QM/MM Approaches for Description of Catalytic Mechanism of Hairpin Ribozyme

We have analyzed the capability of state-of-the-art multiscale computational approaches to provide atomic-resolution electronic structure insights into possible catalytic scenarios of the hairpin ribozyme by evaluating potential and free energy surfaces of the reactions by various hybrid QM/MM methods. The hairpin ribozyme is a unique catalytic RNA that achieves rate acceleration similar to other small self-cleaving ribozymes but without direct metal ion participation. Guanine 8 (G8) and adenine 38 (A38) have been identified as the catalytically essential nucleobases. However, their exact catalytic roles are still being investigated. In line with the available experimental data, we considered two reaction scenarios involving protonated A38H⁺ as a general acid which is further assisted by either canonical G8 or deprotonated G8^– forms. We used the spin-component scaled Møller–Plesset (SCS-MP2) method at the complete basis set limit as the reference method. The semiempirical AM1/d-PhoT and SCC-DFTBPR methods provided acceptable activation barriers with respect to the SCS-MP2 data but predicted significantly different reaction pathways. DFT functionals (BLYP and MPW1K) yielded the same reaction pathway as the SCS-MP2 method. The activation barriers were slightly underestimated by the GGA BLYP functional, although with accuracy comparable to the semiempirical methods. The SCS-MP2 method and hybrid MPW1K functional gave activation barriers that were closest to those derived from experimentally measured rate constants