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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Force Fields in Trouble – What Could Our DNA and RNA Potentials Do Better?

While canonical A-RNA and B-DNA nucleic acid structures seem to be modeled well by current AMBER force fields, the description of non-canonical structures is less satisfactory. This has far-reaching consequences, such as problems with simulations of the nucleic acids folding, which are due to inaccurate description of the unfolded state ensemble. In our laboratory we focus on the development of dihedral angle modifications capable of modeling non-canonical DNA and RNA forms. The key distinguishing feature of our potentials is the inclusion of conformation-dependent solvation effects that were neglected in previous dihedral parameterization efforts. Several modifications now available in the OL15 package (Zgarbova et al., 2015, OL stands for the city of Olomouc, Czech Republic) have shown improvements in modeling of Z-DNA, guanine quadruplexes, non-canonical RNAs as well as canonical A-RNA and B-DNA duplexes. However, current nucleic acid force fields are still far from perfect and many new problems are emerging. One example is the A/B equilibrium in DNA, which is not reproduced by any of the current AMBER force fields (Zgarbova et al., 2018). Another is excessive destabilization of some important naturally occurring α/γ backbone substates in RNA (Zgarbova et al., 2017). Although some of these problems may be solvable by further dihedral angle refinement, it becomes increasingly clear that balance between hydrogen bonding, stacking and interaction with water will have to be tuned to fully explore accuracy potential of the current non-polarizable force fields.

The authors gratefully acknowledge the support by the Czech Science Foundation no. 17-16107S and by the Operational Programme Research, Development and Education – European Regional Development Fund project no. CZ.02.1.01/0.0/0.0/16_019/0000754.

References

    Zgarbova, M.; Sponer, J.; Otyepka, M.; Cheatham, T. E. III; Galindo-Murillo, R.; Jurecka, P. (2015). Refinement of the Sugar−Phosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B‑DNA J. Comput. Theory Chem. 11, 5723-5736.

    Zgarbova, M.; Jurecka, P.; Banas, P.; Havrila, M.; Sponer, J.; Otyepka, M. (2018). A- to B‑DNA Transition in AMBER Force Fields and Its Coupling to Sugar Pucker J. Phys. Chem. B 121, 2420−2433.

    Zgarbova, M.; Jurecka, P.; Sponer, J.; Otyepka, M. (2017). Noncanonical α/γ Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field J. Chem. Theory Comput. 14, 319−328.

Petr Jurečkaa
Marie Zgarbová a
Jiří Šponer a,b
Michal Otyepkaa,

jurecka-petr-photo.gif

Petr Jurecka received his Ph.D. at the Academy of Sciences of the Czech Republic, under prof. Pavel Hobza in 2004. After his postdoctoral stay with Professor D. R. Salahub at the University of Calgary he returned to the Czech Republic, currently. He will provide a short oral from the platform.

aRegional Centre of Advanced Technologies and Materials
Department of Physical Chemistry
Faculty of Science
Palacky University
17. listopadu 12
77146 Olomouc, Czech Republic

bInstitute of Biophysics of the Czech Academy of Sciences,
Královopolská 135
612 65 Brno, Czech Republic

Ph: (+420) 585 634 760
Fx: (+420) 585 634 761
Email: petr.jurecka@upol.cz