  Solvent can occupy up to ~70% of macromolecular crystals and hence having
models that predict solvent distributions in periodic systems could improve in
the interpretation of crystallographic data. Yet there are few implicit solvent
models applicable to periodic solutes while crystallographic structures are
commonly solved assuming a flat solvent model. Here we present a
newly-developed periodic version of the 3D-RISM integral equation method that
is able to solve for efficiently and describe accurately water and ions
distributions in periodic systems; the code can compute accurate gradients that
can be used in minimizations or molecular dynamics simulations. The new method
includes an extension of the OZ equation needed to yield charge neutrality for
charged solutes which requires an additional contribution to the excess
chemical potential that has not been previously identified; this is an
important consideration for nucleic acids or any other charged system where
most or all of the counter- and co-ions are part of the "disordered" solvent.
We present of several calculations of protein, RNA and small molecule crystals
to show that X-ray scattering intensities and solvent structure predicted by
the periodic 3D-RISM solvent model are in closer agreement with experiment than
are intensities computed using the default flat solvent model in the refmac5 or
phenix refinement programs, with the greatest improvement in the 2 to 4 {\AA}
range. Prospects for incorporating integral equation models into
crystallographic refinement are discussed.

Chemical Physics;Biological Physics;Computational Physics