Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique,

13 rue Pierre et Marie Curie, 75005 Paris, France

duboue-dijon@ibpc.fr

Ion–biomolecule interactions are ubiquitous and play a central role in a number of fundamental biological processes, from calcium signaling to Mg²⁺-dependent activity of ribozymes and the formation of DNA–protein complexes. Molecular level understanding of these key biological processes requires to characterize the interaction between proteins or nucleic acids and divalent cations, which is both an experimental and computational challenge. Indeed, only limited reference experimental data are available, and standard biomolecular simulations using non-polarizable force fields suffer from severe overbinding artifacts, especially with divalent cations such as Ca²⁺ and Mg²⁺.

            Our strategy is to develop a scaled charge description of ions and charged biomolecular groups, which takes into account electronic polarization in a mean field way [1-3]. This approach is demonstrated on small model systems, where simulation results can be directly compared both to experimental data (e.g. neutron scattering, capillary electrophoresis, binding free energy estimates) and to reference high-level ab initio calculations or explicitly polarizable force fields. We show that it successfully improves ion-binding properties to proteins [4] and model phosphate groups, and also allows a more accurate description of the strength of salt bridges [5]. This method thus opens the way to large-scale, accurate, and computationally cheap simulations of divalent cation containing biosystems.

References:

[1] I. Leontyev, A. Stuchebrukhov, Phys. Chem. Chem. Phys., 13, 2613 (2011).

[2] T. Martinek, E. Duboué-Dijon,…, P. Jungwirth, J. Chem. Phys., 148, 222813 (2018).

[3] E. Duboué-Dijon, P.E. Mason, …, P. Jungwirth, J. Phys. Chem. B, 122, 3296 (2017)

[4] E. Duboué-Dijon, P. Delcroix,…, P. Jungwirth, J. Phys. Chem. B, 122, 5640 (2018).

[5] P.E. Mason, P. Jungwirth, E. Duboué-Dijon, J. Phys. Chem. Lett., 10, 3254 (2019).