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Title: Numerical calculation of protein-ligand binding rates through solution of the Smoluchowski equation using smoothed particle hydrodynamics

Background: The calculation of diffusion-controlled ligand binding rates is important for understanding enzyme mechanisms as well as designing enzyme inhibitors. Methods: We demonstrate the accuracy and effectiveness of a Lagrangian particle-based method, smoothed particle hydrodynamics (SPH), to study diffusion in biomolecular systems by numerically solving the time-dependent Smoluchowski equation for continuum diffusion. Unlike previous studies, a reactive Robin boundary condition (BC), rather than the absolute absorbing (Dirichlet) BC, is considered on the reactive boundaries. This new BC treatment allows for the analysis of enzymes with “imperfect” reaction rates. Results: The numerical method is first verified in simple systems and then applied to the calculation of ligand binding to a mouse acetylcholinesterase (mAChE) monomer. Rates for inhibitor binding to mAChE are calculated at various ionic strengths and compared with experiment and other numerical methods. We find that imposition of the Robin BC improves agreement between calculated and experimental reaction rates. Conclusions: Although this initial application focuses on a single monomer system, our new method provides a framework to explore broader applications of SPH in larger-scale biomolecular complexes by taking advantage of its Lagrangian particle-based nature.
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  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
BMC Biophysics
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2046-1682
BioMed Central
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR) (SC-21)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES Diffusion, Smoluchowski equation, Smoothed particle hydrodynamics, Protein-ligand interactions, Binding rates, Acetylcholinesterase