Dataset Information

Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods.

ABSTRACT: The tetramer is the most important form for acetylcholinesterase in physiological conditions, i.e., in the neuromuscular junction and the nervous system. It is important to study the diffusion of acetylcholine to the active sites of the tetrameric enzyme to understand the overall signal transduction process in these cellular components. Crystallographic studies revealed two different forms of tetramers, suggesting a flexible tetramer model for acetylcholinesterase. Using a recently developed finite element solver for the steady-state Smoluchowski equation, we have calculated the reaction rate for three mouse acetylcholinesterase tetramers using these two crystal structures and an intermediate structure as templates. Our results show that the reaction rates differ for different individual active sites in the compact tetramer crystal structure, and the rates are similar for different individual active sites in the other crystal structure and the intermediate structure. In the limit of zero salt, the reaction rates per active site for the tetramers are the same as that for the monomer, whereas at higher ionic strength, the rates per active site for the tetramers are approximately 67%-75% of the rate for the monomer. By analyzing the effect of electrostatic forces on ACh diffusion, we find that electrostatic forces play an even more important role for the tetramers than for the monomer. This study also shows that the finite element solver is well suited for solving the diffusion problem within complicated geometries.

SUBMITTER: Zhang D

PROVIDER: S-EPMC1305222 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

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Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods.

Zhang Deqiang D Suen Jason J Zhang Yongjie Y Song Yuhua Y Radic Zoran Z Taylor Palmer P Holst Michael J MJ Bajaj Chandrajit C Baker Nathan A NA McCammon J Andrew JA

Biophysical journal 20041230 3

The tetramer is the most important form for acetylcholinesterase in physiological conditions, i.e., in the neuromuscular junction and the nervous system. It is important to study the diffusion of acetylcholine to the active sites of the tetrameric enzyme to understand the overall signal transduction process in these cellular components. Crystallographic studies revealed two different forms of tetramers, suggesting a flexible tetramer model for acetylcholinesterase. Using a recently developed fin ...[more]

PMID: 15626705

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Project description:We consider the design of an effective and reliable adaptive finite element method (AFEM) for the nonlinear Poisson-Boltzmann equation (PBE). We first examine the two-term regularization technique for the continuous problem recently proposed by Chen, Holst, and Xu based on the removal of the singular electrostatic potential inside biomolecules; this technique made possible the development of the first complete solution and approximation theory for the Poisson-Boltzmann equation, the first provably convergent discretization, and also allowed for the development of a provably convergent AFEM. However, in practical implementation, this two-term regularization exhibits numerical instability. Therefore, we examine a variation of this regularization technique which can be shown to be less susceptible to such instability. We establish a priori estimates and other basic results for the continuous regularized problem, as well as for Galerkin finite element approximations. We show that the new approach produces regularized continuous and discrete problems with the same mathematical advantages of the original regularization. We then design an AFEM scheme for the new regularized problem, and show that the resulting AFEM scheme is accurate and reliable, by proving a contraction result for the error. This result, which is one of the first results of this type for nonlinear elliptic problems, is based on using continuous and discrete a priori L(∞) estimates to establish quasi-orthogonality. To provide a high-quality geometric model as input to the AFEM algorithm, we also describe a class of feature-preserving adaptive mesh generation algorithms designed specifically for constructing meshes of biomolecular structures, based on the intrinsic local structure tensor of the molecular surface. All of the algorithms described in the article are implemented in the Finite Element Toolkit (FETK), developed and maintained at UCSD. The stability advantages of the new regularization scheme are demonstrated with FETK through comparisons with the original regularization approach for a model problem. The convergence and accuracy of the overall AFEM algorithm is also illustrated by numerical approximation of electrostatic solvation energy for an insulin protein.

Project description:PurposeThe study presents an averaged anterior eye geometry model combined with a localised material model that is straightforward, appropriate and amenable for implementation in finite element (FE) modelling.MethodsBoth right and left eye profile data of 118 subjects (63 females and 55 males) aged 22-67 years (38.5 ± 7.6) were used to build an averaged geometry model. Parametric representation of the averaged geometry model was achieved through two polynomials dividing the eye into three smoothly connected volumes. This study utilised the collagen microstructure x-ray data of 6 ex-vivo healthy human eyes, 3 right eyes and 3 left eyes in pairs from 3 donors, 1 male and 2 females aged between 60 and 80 years, to build a localised element-specific material model for the eye.ResultsFitting the cornea and the posterior sclera sections to a 5th-order Zernike polynomial resulted in 21 coefficients. The averaged anterior eye geometry model recorded a limbus tangent angle of 37° at a radius of 6.6 mm from the corneal apex. In terms of material models, the difference between the stresses generated in the inflation simulation up to 15 mmHg in the ring-segmented material model and localised element-specific material model were significantly different (p < 0.001) with the ring-segmented material model recording average Von-Mises stress 0.0168 ± 0.0046 MPa and the localised element-specific material model recording average Von-Mises stress 0.0144 ± 0.0025 MPa.ConclusionsThe study illustrates an averaged geometry model of the anterior human eye that is easy to generate through two parametric equations. This model is combined with a localised material model that can be used either parametrically through a Zernike fitted polynomial or non-parametrically as a function of the azimuth angle and the elevation angle of the eye globe. Both averaged geometry and localised material models were built in a way that makes them easy to implement in FE analysis without additional computation cost compared to the limbal discontinuity so-called idealised eye geometry model or ring-segmented material model.

Dataset Information

Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods.

Publications

Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods.

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