Albany 2015:Book of Abstracts
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., 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
1 Regional Centre of Advanced Technologies and Materials