Water and ions play a fundamental role in the structure, stability, and interactions of biomolecules such as proteins and DNA.
However,     accurately modeling solvent distribution, forces, and thermodynamics with molecular detail remains a computational
challenge. Here we present an overview of the 3D reference interaction site model (3D-RISM) theory of molecular solvation and
how we have used it to understand the so    lvent structure and thermodynamics of DNA, proteins, and small molecules. Examples
will include the macroscopic and microscopic aggregation of ions around DNA, the decomposition of solvation free energy into
polar/nonpolar and energy/entropy, and the spatial decomposition of solvat    ion thermodynamics to identify essential water
molecules in a protein binding site. These examples demonstrate how 3D-RISM, as a molecular implicit solvation model, can
provide quantitative insights into the role of solvent in chemical interactions.