Finite element analysis of the time-dependent Smoluchowski equation for acetylcholinesterase reaction rate calculations.
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.
Cheng
Yuhui
Y
Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California, USA. ycheng@mccammon.ucsd.edu
Suen
Jason K
JK
Zhang
Deqiang
D
Bond
Stephen D
SD
Zhang
Yongjie
Y
Song
Yuhua
Y
Baker
Nathan A
NA
Bajaj
Chandrajit L
CL
Holst
Michael J
MJ
McCammon
J Andrew
JA
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
D000110:Acetylcholinesterase