Diffusion theory can be applied to antibodies attaching to ligand sites

AbstractHumoral immunity is that aspect of specific immunity that is mediated by B lymphocytes and involves the neutralising of disease-producing microorganisms, called pathogens, by means of antibodies attaching to the pathogen's binding sites. This inhibits the pathogen's entry into target cells. We present a master equation in both discrete and in continuous form for a ligand bound atnsites becoming a ligand bound atmsites in a given interaction time. To track the time-evolution of the antibody-ligand interaction, it is shown that the process is most easily treated classically and that in this case the master equation can be reduced to an equivalent one-dimensional diffusion equation. Thus well-known diffusion theory can be applied to antibody-ligand interactions. We consider three distinct cases depending on whether the probability of antibody binding compared to the probability of dissociation is relatively large, small or comparable, and numerical solutions are given.

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Diffusion-Limited Cell Dehydration: Analytical and Numerical Solutions for a Planar Model

10.1115/imece1999-0600 ◽

1999 ◽

Author(s):

Alexander V. Kasharin ◽

Jens O. M. Karlsson

Keyword(s):

Analytical Solution ◽

Numerical Solutions ◽

Planar System ◽

One Dimensional ◽

Diffusion Limited ◽

Dimensional Diffusion ◽

Constant Diffusivity ◽

A Cell ◽

Cell Dehydration ◽

The One

Abstract The process of diffusion-limited cell dehydration is modeled for a planar system by writing the one-dimensional diffusion-equation for a cell with moving, semipermeable boundaries. For the simplifying case of isothermal dehydration with constant diffusivity, an approximate analytical solution is obtained by linearizing the governing partial differential equations. The general problem must be solved numerically. The Forward Time Center Space (FTCS) and Crank-Nicholson differencing schemes are implemented, and evaluated by comparison with the analytical solution. Putative stability criteria for the two algorithms are proposed based on numerical experiments, and the Crank-Nicholson method is shown to be accurate for a mesh with as few as six nodes.

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Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis

10.20944/preprints201912.0374.v1 ◽

2019 ◽

Author(s):

Nurbubu T. Moldogazieva ◽

Daria S. Ostroverkhova ◽

Nikolai N. Kuzmich ◽

Vladimir V. Kadochnikov ◽

Alexander A. Terentiev ◽

...

Keyword(s):

Binding Sites ◽

In Silico ◽

Disulfide Bonds ◽

Electrostatic Interactions ◽

Molecular Mechanisms ◽

3D Structure ◽

Scoring Function ◽

Alpha Fetoprotein ◽

Ligand Interaction ◽

Ligand Interactions

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔGbind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

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Elucidating Binding Sites and Affinities of ERα Agonists and Antagonists to Human Alpha-Fetoprotein by In Silico Modeling and Point Mutagenesis

International Journal of Molecular Sciences ◽

10.3390/ijms21030893 ◽

2020 ◽

Vol 21 (3) ◽

pp. 893 ◽

Cited By ~ 3

Author(s):

Nurbubu T. Moldogazieva ◽

Daria S. Ostroverkhova ◽

Nikolai N. Kuzmich ◽

Vladimir V. Kadochnikov ◽

Alexander A. Terentiev ◽

...

Keyword(s):

Binding Sites ◽

In Silico ◽

Electrostatic Interactions ◽

Molecular Mechanisms ◽

3D Structure ◽

Alpha Fetoprotein ◽

Affinity Binding ◽

Scoring Functions ◽

Ligand Interaction ◽

Ligand Interactions

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting a variety of hydrophobic ligands, including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth, which can be attributed to its estrogen-binding ability. Despite AFP having long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP–ligand interaction remains obscure. In our study, we constructed a homology-based 3D model of human AFP (HAFP) with the purpose of molecular docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol), and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on the ligand-docked scoring functions, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity binding sites were located (i) in a tunnel formed within HAFP subdomains IB and IIA and (ii) on the opposite side of the molecule in a groove originating from a cavity formed between domains I and III, while (iii) the third low-affinity binding site was found at the bottom of the cavity. Here, 100 ns molecular dynamics (MD) simulation allowed us to study their geometries and showed that HAFP–estrogen interactions were caused by van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP–antiestrogen binding. Molecular mechanics/Generalized Born surface area (MM/GBSA) rescoring method exploited for estimation of binding free energies (ΔGbind) showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP–ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues, along with two disulfide bonds (Cys224–Cys270 and Cys269–Cys277), have key roles in both HAFP–estrogen and HAFP–antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein–ligand interactions and anticancer therapy strategies based on ERα-binding ligands.

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Feller’s Contributions to the One-Dimensional Diffusion Theory and Beyond

Selected Papers II ◽

10.1007/978-3-319-16856-2_4 ◽

2015 ◽

pp. 63-76

Author(s):

Masatoshi Fukushima

Keyword(s):

Diffusion Theory ◽

One Dimensional ◽

Dimensional Diffusion ◽

The One

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Comparison of Vacancy Sink Efficiency of Cu/V and Cu/Nb Interfaces by the Shared Cu Layer

Materials ◽

10.3390/ma12162628 ◽

2019 ◽

Vol 12 (16) ◽

pp. 2628 ◽

Cited By ~ 1

Author(s):

Huaqiang Chen ◽

Jinlong Du ◽

Yanxia Liang ◽

Peipei Wang ◽

Jinchi Huang ◽

...

Keyword(s):

Incident Energy ◽

Diffusion Theory ◽

New Method ◽

Helium Ions ◽

Helium Concentration ◽

One Dimensional ◽

Helium Bubbles ◽

Dimensional Diffusion ◽

Multilayer Composites

This paper provides a new method to compare and then reveal the vacancy sink efficiencies quantitively between different hetero-interfaces with a shared Cu layer in one sample, in contrast to previous studies, which have compared the vacancy sink efficiencies of interfaces in different samples. Cu-Nb-Cu-V nanoscale metallic multilayer composites (NMMCs) containing Cu/V and Cu/Nb interfaces periodically were prepared as research samples and bombarded with helium ions to create vacancies which were filled by helium bubbles. A special Cu layer shared by adjoining Cu/V and Cu/Nb interfaces exists, in which the implanted helium concentration reaches its maximum and remains nearly constant with a well-designed incident energy. The results show that bubble-denuded zones (BDZ) close to interfaces exist, and that the width of the BDZ close to the Cu/V interface is less than that of Cu/Nb interface. This result is explained by one-dimensional diffusion theory, and the ratio of vacancy sink efficiency between Cu/V and Cu/Nb interfaces is calculated. Conclusively, Cu/Nb interfaces are more efficient than Cu/V interfaces in eliminating vacancies induced by radiation.

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