Implicit Solvent\nwith Explicit Ions Generalized Born\nModel in Molecular Dynamics: Application to DNA

The ion atmosphere\nsurrounding highly charged biomolecules,\nsuch\nas nucleic acids, is crucial for their dynamics, structure, and interactions.\nHere, we develop an approach for the explicit treatment of ions within\nan implicit solvent framework suitable for atomistic simulations of\nbiomolecules. The proposed implicit solvent/explicit ions model, GBION, is based on a modified generalized Born (GB)\nmodel; it includes separate, modified GB terms for solute–ion\nand ion–ion interactions. The model is implemented in the AMBER\npackage (version 24), and its performance is thoroughly investigated\nin atomistic molecular dynamics (MD) simulations of double-stranded\nDNA on a microsecond time scale. The aggregate characteristics of\nmonovalent (Na<sup>+</sup> and K<sup>+</sup>) and trivalent (Cobalt\nHexammine, CoHex<sup>3+</sup>) counterion distributions around double-stranded\nDNA predicted by the model are in reasonable agreement with the experiment\n(where available), all-atom explicit water MD simulations, and the\nexpectation from the Manning condensation theory. The radial distributions\nof monovalent cations around DNA are reasonably close to the ones\nobtained using the explicit water model: expressed in units of energy,\nthe maximum deviations of local ion concentrations from the explicit\nsolvent reference are within 1 <i>k</i><sub>B</sub><i>T</i>, comparable to the corresponding deviations expected between\ndifferent established explicit water models. The proposed GBION model is able to simulate DNA fragments in a large\nvolume of solvent with explicit ions with little additional computational\noverhead compared with the fully implicit GB treatment of ions. Ions\nsimulated using the developed model explore conformational space at\nleast 2 orders of magnitude faster than in the explicit solvent. These\nadvantages allowed us to observe and explore an unexpected “stacking”\nmode of DNA condensation in the presence of trivalent counterions\n(CoHex<sup>3+</sup>) that was revealed by recent experiments.