Comparative Assessment of Different RNA Tetranucleotides from the DFT-D3 and Force Field Perspective

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Authors

SZABLA Rafal HAVRILA Marek KRUSE Holger ŠPONER Jiří

Year of publication 2016
Type Article in Periodical
Magazine / Source Journal of Physical Chemistry B
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://pubs.acs.org/doi/abs/10.1021/acs.jpcb.6b07551
Doi http://dx.doi.org/10.1021/acs.jpcb.6b07551
Field Physical chemistry and theoretical chemistry
Keywords MOLECULAR-DYNAMICS SIMULATIONS; QUANTUM-CHEMICAL COMPUTATIONS; AUXILIARY BASIS-SETS; PARTICLE MESH EWALD; DIRECT-COSMO-RS; B-DNA STRUCTURE; PHOSPHATE BACKBONE; EXPLICIT-SOLVENT; NUCLEIC-ACIDS; FREE-ENERGIES
Description Classical force field (FF) molecular dynamics (MD) simulations of RNA tetranucleotides have substantial problems in reproducing conformer populations indicated by NMR experiments. To provide more information about the possible sources of errors, we performed quantum mechanical (QM, TPSS-D3/def2-TZVP) and molecular mechanics (MM, AMBER parm99bsc0+X-OL3) calculations of different r(CCCC), r(GACC), and r(UUUU) conformers obtained from explicit solvent MD simulations. Solvent effects in the static QM and MM calculations were mimicked using implicit solvent models (COSMO and Poisson-Boltzmann, respectively). The comparison of QM and MM geometries and energies revealed that the two methodologies provide qualitatively consistent results in most of the cases. Even though we found some differences, these were insufficient to indicate any systematic corrections of the RNA FF terms that could improve the performance of classical MD in simulating tetranucleotides. On the basis of these findings, we inferred that the overpopulation of intercalated conformers in the MD simulations of RNA tetramers, which were not observed experimentally, might be predominantly caused by imbalanced water-solvent and water-water interactions. Apart from the large-scale QM calculations performed to assess the performance of the AMBER FF, a representative spectrum of faster QM methods was tested.
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