Hierarchical Molecular Interfaces and Solvation

Electrostatic interactions play a significant role in determin-ing the binding affinity of molecules and drugs. While signif-icant effort has been devoted to the accurate computation of biomolecular electrostatics based on an all-atomic solu-tion of the Poisson-Boltzmann (PB) equation for smaller proteins and nucleic acids, relatively little has been done to optimize the efficiency of electrostatic energetics and force computations of macromolecules at varying resolutions (also called coarse-graining). We have developed an efficient and comprehensive framework for computing coarse-grained PB electrostatic potentials, polarization energetics and forces for smooth multi-resolution representations of almost all molec-ular structures, available in the PDB. Important aspects of our framework include the use of variational methods for generating C2-smooth and multi-resolution molecular sur-faces (as dielectric interfaces), a parameterization and dis-cretization of the PB equation using an algebraic spline boundary element method, and the rapid estimation of the electrostatic energetics and forces using a kernel independent fast multipole method. We present details of our implemen-tation, as well as several performance results on a number of examples. 1