The matrices S and D are discretized forms of the socalled single-and double-layer operators, Ŝ and D. The former generates the surface electrostatic potential, and its matrix representation S consists of the Coulomb interaction between surface elements. The operator D † generates the normal electric field at the cavity surface. The IEF-PCM version of Poisson's equation provides a theoretical basis for several other approaches to implicit solvation including Generalized Born models and Debye-Hückel theory. Replacing DAS in eq. 4 with (DAS + SAD † )/2 affords the surface and simulation of volume polarization for electrostatics [SS(V)PE] method, which is formally equivalent to IEF-PCM at the level of integral equations. However, the SS(V)PE form is more sensitive to the quality of the surface discretization and may exhibit numerical artifacts at "crevices" between atomic spheres. These artifacts generally disappear for larger atomic spheres, which afford smoother cavities, but for this reason we will use the IEF-PCM form exclusively.