cancellation at large distances—two neutral molecules interact via a dipole-dipole term which varies as $1/r^3$, while the individual atom-atom terms decay as $1/r_{ij}$. In this case, we need to identify groups of atoms which should interact together. The residues of a protein provide a convenient grouping and we would typically assign all the atoms in a small-molecule ligand to a single group. Compatible with the usage for a protein, we refer to these groups as residues. For each residue, $s$, we define a center position, $\v b_s$, most conveniently defined as the center of mass, and a radius, defined as the radius $h_s$ of the sphere centered at $\v b_s$ which includes the van-der-Waals spheres of radius $\rho_i$ of all the constituent atoms. We then apply a “per-residue” cutoff function multiplying the contribution from the residue pair $(s,t)$ by $c_g(\abs{\v b_s - \v b_t} - (h_s + h_t))$.

The values used for the cutoff radii, $r_{g1}$ and $r_{g2}$, need to evaluated based on the accuracy desired for the simulation. This can be determined by numerically determining the difference in the results (either for the energies directly or for some derived quantity such as binding affinity) between the finite- and infinite-cutoff 