This article describes the development and implementation of algorithms to study diffusion in biomolecular systems using continuum mechanics equations. Specifically, finite element methods have been developed to solve the steady-state Smoluchowski equation to calculate ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to mouse acetylcholinesterase. Rates for inhibitor binding to mAChE were calculated at various ionic strengths with several different reaction criteria. The calculated rates were compared with experimental data and show very good agreement when the correct reaction criterion is used. Additionally, these finite element methods require significantly less computational resources than existing particle-based Brownian dynamics methods.
Song, Y., Zhang, Y., Shen, T., Bajaj, C. L., McCammon, J. A., & Baker, N. A. (2004). Finite Element Solution of the Steady-State Smoluchowski Equation for Rate Constant Calculations. Biophysical Journal, 86(4), 2017–2029. https://doi.org/10.1016/S0006-3495(04)74263-0