Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Deriving and Testing Force Field Torsion Parameters for RNA and DNA Simulations

We present extensive testing of three recently developed force field modifications for DNA and RNA simulations based on AMBER force field, namely modifications of the glycosidic torsion chi (χOL3 and χOL4), and sugar-phosphate backbone torsions epsilon and zeta (ϵζOL1). All these modifications were derived using a parameterization procedure that includes certain previously neglected conformation-dependent solvation effects (Zgarbova et al., 2012). We show that the conformation-dependent solvation contribution is substantial and provides important corrections to the torsion potentials that lead to improved description of structure and dynamics of nucleic acids in molecular dynamics simulations. The glycosidic potential χOL3 has been shown to prevent formation of spurious "ladder-like" structures in RNA helices (Zgarbova et al., 2011) and the χOL4 modification aimed at better description of guanines in the (χ=syn state found for instance in DNA quadruplexes or Z-DNA (Krepl et al., 2012). Here we focus on the epsilon and zeta modification, ϵζOL1 (Zgarbova et al., 2013), which was designed to improve description of DNA backbone. Our modification increases the overall helical twist, improves its sequence dependence, lowers RMDS of the sugar-phosphate backbone with respect to the X-ray reference and improves description of the groove widths. In addition, the balance between populations of the BI and BII backbone substates is shifted towards the BII state, in better agreement with the ensemble-refined solution NMR results. Additional tests are presented for DNA A-tracts (Drsata et al. 2014), DNA and RNA fraying, G-DNA, Z-DNA and RNA ribozyme.

    Zgarbova, M., Luque, F. J., Sponer, J., Otyepka, M., Jurecka, P. (2012) Novel Approach for Deriving Force Field Torsion Angle Parameters Accounting for Conformation-Dependent Solvation Effects J. Chem. Theory Comput. 8 (9), 3232-3242.

    Zgarbova, M., Otyepka, M., Sponer, J., Mladek, A., Banas, P., Cheatham, T. E., Jurecka, P. (2011). Refinement of the Cornell et al. nucleic acid force field based on reference quantum chemical calculations of torsion profiles of the glycosidic torsion. Journal J. Chem. Theory Comput. 7, 2886-2902.

    Krepl, M., Zgarbova, M., Stadlbauer, P., Otyepka, M., Banas, P., Koca, J., Cheatham, T.E., Jurecka, P., Sponer, J. (2012). Reference simulations of noncanonical nucleic acids with different chi variants of the AMBER force field: Quadruplex DNA, quadruplex RNA, and Z-DNA. J. Chem. Theory Comput. 8, 2506-2520.

    Zgarbova, M., Luque, F. J., Sponer, J., Cheatham, T. E., Otyepka, M., Jurecka, P. (2013) Toward Improved Description of DNA Backbone: Revisiting Epsilon and Zeta Torsion Force Field Parameters J. Chem. Theory Comput. 9 (5), 2339-2354.

    Drsata, T., Spackova, N., Jurecka, P., Zgarbova, M., Sponer, J., Lankas, F. (2014) Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning Nucleic Acids Res. 42 (11), 7383-7394.

Petr Jurecka 1
Marie Zgarbova1
Pavel Banas1
Michal Otyepka1
F. Javier Luque2
Thomas E. Cheatham, III3
Jiri Sponer4
Filip Lankas5

1 Regional Centre of Advanced Technologies and Materials
Department of Physical Chemistry
Faculty of Science
Palacky University
17. listopadu 12
77146 Olomouc, Czech Republic
2 Department de Fisicoquímica and Institut de Biomedicina (IBUB)
Facultat de Farmàcia
Universitat de Barcelona
Avgda Diagonal 643
Barcelona 08028, Spain
3 Department of Medicinal Chemistry
College of Pharmacy
University of Utah
Salt Lake City, Utah, US
4 Institute of Biophysics
Academy of Sciences of the Czech Republic
Královopolska 135
612 65 Brno, Czech Republic
5 Institute of Organic Chemistry and Biochemistry
Academy of Sciences of the Czech Republic
Flemingovo nam. 2
16610 Prague, Czech Republic

Phone: (420) 585 634 760
Email: petr.jurecka@upol.cz,