  In multi-resolution simulations, different system components are
simultaneously modelled at different levels of resolution, these being smoothly
coupled together. In the case of enzyme systems, computationally expensive
atomistic detail is needed in the active site to capture the chemistry of
substrate binding. Global properties of the rest of the protein also play an
essential role, determining the structure and fluctuations of the binding site;
however, these can be modelled on a coarser level. Similarly, in the most
computationally efficient scheme only the solvent hydrating the active site
requires atomistic detail. We present a methodology to couple atomistic and
coarse-grained protein models, while solvating the atomistic part of the
protein in atomistic water. This allows a free choice of which protein and
solvent degrees of freedom to include atomistically, without loss of accuracy
in the atomistic description. This multi-resolution methodology can
successfully model stable ligand binding, and we further confirm its validity
via an exploration of system properties relevant to enzymatic function. In
addition to a computational speedup, such an approach can allow the
identification of the essential degrees of freedom playing a role in a given
process, potentially yielding new insights into biomolecular function.
