Construction and Refinements of a Polarizable Molecular Mechanics/Dynamics Potential for Large-Scale Simulations of DNA and RNA
Nohad Gresh1*, Sehr Naseem-Khan1, Louis Lagardère1, Judit E. Sponer2, Jiri Sponer2,3, Jean-Philip Piquemal1
1Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC, UMR7616 CNRS, Paris, France
2Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovpolska 135, 612 65 Brno, Czech Republic
3 CEITEC – Central European Institute of Technology, Masaryk University, Campus Bohunice, Kamenice 5, 625 00 Brno, Czech Republic
*
We report recent ab initio QC validations of the SIBFA polarizable molecular mechanics procedure [1] in view of large-scale molecular dynamics (MD) of DNA and RNA. Earlier validations bore on divalent cation complexes of the DNA base-pairs [2] and of 5’-guanosine monophosphate [3]. We present validations bearing on stacked and H-bonded complexes of cytosine and guanine [4] and on the channeling of alkali cations (Li+, Na+, K+ and Rb+) across two stacked guanine tetramers [5]. The dimethyl phosphate anion (DMP-), a pivotal unit of the sugar-phosphate backbone, is subsequently probed in detail by a divalent cation or by water binding in a mono- or bidentate coordination to its anionic and/or ester oxygens. Issues such as anomeric effects and multipole transferability upon conformational changes are addressed. Perspectives of extension to DNA and RNA oligomers, as well as drug binding, are considered.
Figure 1.Evolutions of the CCSD(T) and SIBFA interaction energies.
References.
[1] Gresh, N.; Cisneros, G. A.; Darden, T. A.; Piquemal, J.-P. Anisotropic, Polarizable Molecular Mechanics Studies of Inter- and Intramolecular Interactions and Ligand−Macromolecule Complexes. A Bottom-Up Strategy.Journal of Chemical Theory and Computation 2007,3, 1960-1986.
[2] Gresh, N., Sponer, J. Complexes of pentahydrated Zn2+ with guanine, adenine, and the guanine-cytosine and adenine-thymine base-. Gresh, and J. Sponer, TheJournal of Physical Chemistry B, 1999,103, 11415-11427.
[3] Gresh, N.; Šponer, J. E.; Špačková, N. a.; Leszczynski, J.; Šponer, J. Theoretical Study of Binding of Hydrated Zn(II) and Mg(II) Cations to 5‘-Guanosine Monophosphate. Toward Polarizable Molecular Mechanics for DNA and RNA.The Journal of Physical Chemistry B 2003,107, 8669-8681.
[4] Gresh, N.; Sponer, J. E.; Devereux, M.; Gkionis, K.; de Courcy, B.; Piquemal, J.-P.; Sponer, J., Stacked and H-Bonded Cytosine Dimers. Analysis of the Intermolecular Interaction Energies by Parallel Quantum Chemistry and Polarizable Molecular Mechanics.The Journal of Physical Chemistry B 2015,119, 9477-9495.
[5] Gresh, N., Naseem-Khan, S, Lagardère, L., Piquemal, J.-P., Sponer, J.E., Sponer, J. Channeling Through Two Stacked Guanine Quartets of One and Two Alkali Cations in the Li+, Na+, K+ and Rb+ Series. Assessment of the Accuracy of the SIBFA Anisotropic Polarizable Molecular Mechanics Potential..The Journal of Physical Chemistry B,2017, 121, 3997-4014
Lorentz Center Leiden 30th October – 3rd November 2017