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Structural study of biologically significant ligands with major birch pollen allergen Betv1 by docking and molecular dynamics simulation.

Kundu S, Roy D - Bioinformation (2010)

Bottom Line: In the present study thirteen ligands have been successfully docked into the hydrophobic cavity of Betv1 and binding free energies of the complexes have been calculated using AutoDock 3.0.5.The complex formed between Betv1 and the best docking pose for each ligand has been optimized by molecular dynamics simulation.This knowledge is required for structural alteration or inhibition of some of these ligands in order to modify the allergenic properties of this protein.

View Article: PubMed Central - PubMed

Affiliation: Debjani Roy Bioinformatics Centre, Bose Institute, Acharya J.C Bose Centenary Building, P-1/12 C.I.T Scheme -VII M, Kolkata - 700054 India.

ABSTRACT
The major birch pollen allergen, Betv1 of Betula verrucosa is the main causative agent of birch pollen allergy in humans. Betv1 is capable of binding several physiological ligands including fatty acids, flavones, cytokinins and sterols. Until now, no structural information from crystallography or NMR is available regarding binding mode of any of these ligands into the binding pocket of Betv1. In the present study thirteen ligands have been successfully docked into the hydrophobic cavity of Betv1 and binding free energies of the complexes have been calculated using AutoDock 3.0.5. A linear relationship with correlation coefficient (R²) of 0.6 is obtained between ΔG(b)s values plotted against their corresponding IC50 values. The complex formed between Betv1 and the best docking pose for each ligand has been optimized by molecular dynamics simulation. Here, we describe the ligand binding of Betv1, which provides insight into the biological function of this protein. This knowledge is required for structural alteration or inhibition of some of these ligands in order to modify the allergenic properties of this protein.

No MeSH data available.


Related in: MedlinePlus

(A) Graphical representation of docked orientation of ligands 1, 2 and 7 with Betv1. Compounds 1, 2 and 7 are shown in pink, cyan andblue respectively. (B): Graphical representation of docked orientation of ligands 9, 12 and 13 with Betv1. Compounds 9, 12 and 13 are shown incyan, pink, and blue respectively. P-loop is shown in red.
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Figure 2: (A) Graphical representation of docked orientation of ligands 1, 2 and 7 with Betv1. Compounds 1, 2 and 7 are shown in pink, cyan andblue respectively. (B): Graphical representation of docked orientation of ligands 9, 12 and 13 with Betv1. Compounds 9, 12 and 13 are shown incyan, pink, and blue respectively. P-loop is shown in red.

Mentions: Previous NMR study indicates that fluorescent probe 8-anilino-1-naphthalenesulfonic acid (ANS) binds in the cavity of Betv1 but theauthors did not pinpoint specific ANS binding site [5]. Our docking andsubsequent molecular dynamics simulation result of ANS shows that itis involved in hydrophobic interaction with side-chains of residuesIle23, Phe30, Pro31, Ile38, Val41, Lys54, Ile56, Ile102, Ile116 andLeu143 of Betv1 (Figure 2A). The anilino and naphthalene-sulphonicacid moiety of ANS interact with the side-chain residues of Phe30,Phe58, Tyr81 and Phe22, Phe30, Phe58, Tyr81, Tyr83 respectively viaπ-π interaction. Our result corroborates well with the NMR experimentwhere the perturbed protons are shown to form a large patch along the βsheet and several distinct regions in α–helices [5]. Most of theinteracting residues found in our study also belong to these two regions.


Structural study of biologically significant ligands with major birch pollen allergen Betv1 by docking and molecular dynamics simulation.

Kundu S, Roy D - Bioinformation (2010)

(A) Graphical representation of docked orientation of ligands 1, 2 and 7 with Betv1. Compounds 1, 2 and 7 are shown in pink, cyan andblue respectively. (B): Graphical representation of docked orientation of ligands 9, 12 and 13 with Betv1. Compounds 9, 12 and 13 are shown incyan, pink, and blue respectively. P-loop is shown in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957764&req=5

Figure 2: (A) Graphical representation of docked orientation of ligands 1, 2 and 7 with Betv1. Compounds 1, 2 and 7 are shown in pink, cyan andblue respectively. (B): Graphical representation of docked orientation of ligands 9, 12 and 13 with Betv1. Compounds 9, 12 and 13 are shown incyan, pink, and blue respectively. P-loop is shown in red.
Mentions: Previous NMR study indicates that fluorescent probe 8-anilino-1-naphthalenesulfonic acid (ANS) binds in the cavity of Betv1 but theauthors did not pinpoint specific ANS binding site [5]. Our docking andsubsequent molecular dynamics simulation result of ANS shows that itis involved in hydrophobic interaction with side-chains of residuesIle23, Phe30, Pro31, Ile38, Val41, Lys54, Ile56, Ile102, Ile116 andLeu143 of Betv1 (Figure 2A). The anilino and naphthalene-sulphonicacid moiety of ANS interact with the side-chain residues of Phe30,Phe58, Tyr81 and Phe22, Phe30, Phe58, Tyr81, Tyr83 respectively viaπ-π interaction. Our result corroborates well with the NMR experimentwhere the perturbed protons are shown to form a large patch along the βsheet and several distinct regions in α–helices [5]. Most of theinteracting residues found in our study also belong to these two regions.

Bottom Line: In the present study thirteen ligands have been successfully docked into the hydrophobic cavity of Betv1 and binding free energies of the complexes have been calculated using AutoDock 3.0.5.The complex formed between Betv1 and the best docking pose for each ligand has been optimized by molecular dynamics simulation.This knowledge is required for structural alteration or inhibition of some of these ligands in order to modify the allergenic properties of this protein.

View Article: PubMed Central - PubMed

Affiliation: Debjani Roy Bioinformatics Centre, Bose Institute, Acharya J.C Bose Centenary Building, P-1/12 C.I.T Scheme -VII M, Kolkata - 700054 India.

ABSTRACT
The major birch pollen allergen, Betv1 of Betula verrucosa is the main causative agent of birch pollen allergy in humans. Betv1 is capable of binding several physiological ligands including fatty acids, flavones, cytokinins and sterols. Until now, no structural information from crystallography or NMR is available regarding binding mode of any of these ligands into the binding pocket of Betv1. In the present study thirteen ligands have been successfully docked into the hydrophobic cavity of Betv1 and binding free energies of the complexes have been calculated using AutoDock 3.0.5. A linear relationship with correlation coefficient (R²) of 0.6 is obtained between ΔG(b)s values plotted against their corresponding IC50 values. The complex formed between Betv1 and the best docking pose for each ligand has been optimized by molecular dynamics simulation. Here, we describe the ligand binding of Betv1, which provides insight into the biological function of this protein. This knowledge is required for structural alteration or inhibition of some of these ligands in order to modify the allergenic properties of this protein.

No MeSH data available.


Related in: MedlinePlus