title: Finite element analysis of the time-dependent Smoluchowski equation for acetylcholinesterase reaction rate calculations.
abstract: This article describes the numerical solution of the time-dependent Smoluchowski equation to study diffusion in biomolecular systems. Specifically, finite element methods have been developed to calculate ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to the mouse acetylcholinesterase (mAChE) monomer and several tetramers. Rates for inhibitor binding to mAChE were calculated at various ionic strengths with several different time steps. Calculated rates show very good agreement with experimental and theoretical steady-state 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 rate accelerations of the monomeric and tetrameric mAChE that result from electrostatic steering are preserved under the non-steady-state conditions that are expected to occur in physiological circumstances.
authors.affiliation: Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California, USA. ycheng@mccammon.ucsd.edu
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Jason K
authors.initials: JK
authors.lastname: Suen
authors.forename: Deqiang
authors.initials: D
authors.lastname: Zhang
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bond
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Song
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Baker
authors.forename: Chandrajit L
authors.initials: CL
authors.lastname: Bajaj
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holst
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000648:ultrastructure*; D000465:Algorithms; D003198:Computer Simulation; D004058:Diffusion; D004789:Enzyme Activation; D020342:Finite Element Analysis; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D000110:Acetylcholinesterase