Dataset Information

Finite element analysis of drug electrostatic diffusion: inhibition rate studies in N1 neuraminidase.

ABSTRACT: This article describes a numerical solution of the steady-state Poisson-Boltzmann-Smoluchowski (PBS) and Poisson-Nernst-Planck (PNP) equations to study diffusion in biomolecular systems. Specifically, finite element methods have been developed to calculate electrostatic interactions and ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to the wild-type and several mutated avian influenza neurominidase crystal structures. The calculated rates show very good agreement with recent experimental 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 electrostatic steering plays the important role in the drug binding process of the neurominidase.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC3107071 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Finite element analysis of drug electrostatic diffusion: inhibition rate studies in N1 neuraminidase.

Cheng Yuhui Y Holst Michael J MJ McCammon J A JA

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 20090101

This article describes a numerical solution of the steady-state Poisson-Boltzmann-Smoluchowski (PBS) and Poisson-Nernst-Planck (PNP) equations to study diffusion in biomolecular systems. Specifically, finite element methods have been developed to calculate electrostatic interactions and ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to the wild-type and several mutated avian influenza neurominidase crystal structures. The calculated ra ...[more]

PMID: 19209708

Similar Datasets

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

Finite element analysis of drug electrostatic diffusion: inhibition rate studies in N1 neuraminidase.

Publications

Finite element analysis of drug electrostatic diffusion: inhibition rate studies in N1 neuraminidase.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets