Multimolecular complexes of the phosphodiester anion with Zn(II) or Mg(II) and water molecules—Preliminary validations of a polarizable potential by ab initio quantum chemistry

Abstract

Dimethyl phosphate (DMP−) is a model for the phosphodiester backbone of DNA, RNA, and phospholipids. It is central for the binding of divalent cations and water along the backbone of nucleic acids. Significant polarization and charge‐transfer contributions and nonadditivity come into play in the multimolecular complexes organized around phosphate. Prior to large‐scale molecular dynamics (MD) with advanced polarizable potentials, it is essential to evaluate how well the values and trends of intermolecular interaction energies (ΔE) from ab initio quantum chemistry (QC) and their individual contributions are reproduced in a diversity of such complexes. These differ by the starting binding modes of a divalent cation, Zn(II), namely direct, bi‐ or mono‐dentate to anionic and/or ester oxygens, versus through‐water binding. We present first the results from automated refinements of the individual contributions of the SIBFA potential with respect to their QC counterparts using a Zn(II) or a water probe. This is followed by validations on eight relaxed multimolecular complexes of DMP− with Zn(II) or Mg(II) and seven waters, then on sixteen complexes of DMP− with Zn(II) and eight waters in arrangements extracted from MD or energy‐minimization on a droplet of sixty‐four waters. This monitors the compared evolutions of SIBFA and QC ΔE and their individual contributions in the competing arrangements. Some waters, bridging Zn(II) and DMP−, were found to have exceptionally large dipole moments, of up to 3.8 Debye. The perspectives of extension to a flexible phosphodiester backbone are discussed in the context of the SIBFA potential for DNA and RNA.