Finite Element Analysis of Drug Electrostatic Diffusion: Inhibition Rate Studies in N1 Neuraminidase

This article describes a numerical solution of the steady-state Poisson-Boltzmann-Smoluchowski (PBS) and Poisson-Nernst-Planck (PNP) equations to study diffusion in biomolecular systems. Specifically, finite element methods have been developed to calculate electrostatic interactions and ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to the wild-type and several mutated avian influenza neurominidase crystal structures. The calculated rates show very good agreement with recent experimental studies. Furthermore, these finite element methods require significantly fewer computational resources than existing particle-based Brownian dynamics methods and are robust for complicated geometries. The key finding of biological importance is that the electrostatic steering plays the important role in the drug binding process of the neurominidase.