Informace o publikaci

Microsecond-Scale MD Simulations of HIV-1 DIS Kissing-Loop Complexes Predict Bulged-In Conformation of the Bulged Bases and Reveal Interesting Differences between Available Variants of the AMBER RNA Force Fields

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HAVRILA Marek ZGARBOVÁ Marie JUREČKA Petr BANÁŠ Pavel KREPL Miroslav OTYEPKA Michal ŠPONER Jiří

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Physical Chemistry B
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5b08876
Doi http://dx.doi.org/10.1021/acs.jpcb.5b08876
Obor Fyzikální chemie a teoretická chemie
Klíčová slova MOLECULAR-DYNAMICS SIMULATIONS; DIMERIZATION INITIATION SITE; QUANTUM-CHEMICAL COMPUTATIONS; NMR SOLUTION STRUCTURE; 30S RIBOSOMAL-SUBUNIT; PARTICLE MESH EWALD; GENOMIC RNA; REPLICA-EXCHANGE; EXTENDED-DUPLEX; NUCLEIC-ACIDS
Popis We report an extensive set of explicit solvent molecular dynamics (MD) simulations (similar to 25 mu s of accumulated simulation time) of the RNA kissing-loop complex of the HIV-1 virus initiation dimerization site. Despite many structural investigations by X-ray, NMR, and MD techniques, the position of the bulged purines of the kissing complex has not been unambiguously resolved. The X-ray structures consistently show bulged-out positions of the unpaired bases, while several NMR studies show bulged-in conformations. The NMR studies are, however, mutually inconsistent regarding the exact orientations of the bases. The earlier simulation studies predicted the bulged-out conformation; however, this finding could have been biased by the short simulation time scales. Our microsecond-long simulations reveal that all unpaired bases of the kissing-loop complex stay preferably in the interior of the kissing-loop complex. The MD results are discussed in the context of the available experimental data and we suggest that both conformations are biochemically relevant. We also show that MD provides a quite satisfactory description of this RNA system, contrasting recent reports of unsatisfactory performance of the RNA force fields for smaller systems such as tetranucleotides and tetraloops. We explain this by the fact that the kissing complex is primarily stabilized by an extensive network of Watson Crick interactions which are rather well described by the force fields. We tested several different sets of water/ion parameters but they all lead to consistent results. However, we demonstrate that a recently suggested modification of van der Wools interactions of the Cornell et al. force field deteriorates the description of the kissing complex by the loss of key stacking interactions stabilizing the interhelical junction and excessive hydrogen-bonding interactions.
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