Binding of biguanides to β-lactoglobulin: molecular-docking and molecular dynamics simulation studies

Biguanides are a class of drugs derived from biguanide and they are the most widely used drugs for diabetes mellitus or pre-diabetes treatment. An investigation of their interaction and a transport protein such as β-lactoglobulin (BLG) at atomic level could be a valuable factor in controlling their transport to biological sites. Molecular-docking and molecular dynamics simulation methods were used to study the interaction of metformin, phenformin and buformin as biguanides and BLG as transport protein. The molecular-docking results revealed that these biguanides bind to BLG and that the BLG affinity for binding the biguanides decreases in the following order: phenformin — buformin — metformin. The docking results also show the hydrophobic interactions to have a significant role in the BLG-biguanides complex stability. Analysis of molecular dynamic simulation trajectories shows that the root mean square deviation of various systems attained equilibrium and fluctuated around the mean value at various times. The time evolution of the radius of gyration and the total solvent-accessible surface of the protein showed that BLG and BLG-biguanide complexes became stable at approximately 2500 ps and that there was not any conformational change in the BLG-biguanide complexes. In addition, the profiles of atomic fluctuations show the rigidity of the ligand-binding site during the simulation

Atomic insight into designed carbamate-based derivatives as acetylcholine esterase (AChE) inhibitors: a computational study by multiple molecular docking and molecular dynamics simulation

<p>Over 100 variants have been designed and studied, using multiple docking methods such as Autodock Vina, ArgusLab, Molegro Virtual Docker, and Hex-Cuda, to study the effect of alteration in the structure of carbamate-based acetylcholyne esterase (AChE) inhibitors. Sixteen selected systems were then subjected to 14 ns molecular dynamics (MD) simulations. Results from all the docking methods are in agreement. Variants that involved biphenyl substituents possess the most negative binding energies in the −37.64 to −39.31 kJ mol⁻¹ range due to their π–π interactions with AChE aromatic residues. The root mean square deviation values showed that all of these components achieved equilibration after 6 ns. Gyration radius (<i>R</i>_g) and solvent accessibility surface area were calculated to further investigate the AChE conformational changes in the presence of these components. MD simulation results suggested that these components might interact with AChE, possibly with no major changes in AChE secondary and tertiary structures.</p

A computational study to identify the key residues of peroxisome proliferator-activated receptor gamma in the interactions with its antagonists

<p>Peroxisome proliferator-activated receptors (PPARs) compose a family of nuclear receptors, PPARα, PPARβ, and PPARγ, which mediate the effects of lipidic ligands at the transcriptional level. Among these, the PPARγ has been known to regulate adipocyte differentiation, fatty acid storage and glucose metabolism, and is a target of antidiabetic drugs. In this work, the interactions between PPARγ and its six known antagonists were investigated using computational methods such as molecular docking, molecular dynamics (MD) simulations, and the hybrid quantum mechanics/molecular mechanics (QM/MM). The binding energies evaluated by molecular docking varied between −22.59 and −35.15 kJ mol^− 1. In addition, MD simulations were performed to investigate the binding modes and PPARγ conformational changes upon binding of antagonists. Analysis of the root-mean-square fluctuations (<i>RMSF</i>) of backbone atoms shows that H3 of PPARγ has a higher mobility in the absence of antagonists and moderate conformational changes were observed. The interaction energies between antagonists and each PPARγ residue involved in the interactions were studied by QM/MM calculations. These calculations reveal that antagonists with different structures show different interaction energies with the same residue of PPARγ. Therefore, it can be concluded that the key residues vary depending on the structure of the ligand, which binds to PPARγ.</p

Fluorescence spectroscopic study on interaction of retinol with β-lactoglobulin in the presence of cetylpyridinium chloride

International audienceIn our previous study thermodynamic denaturation of bovine β-lactoglobulin variant A (BLG-A), has been investigated in the presence of cetylpyridinium chloride (CPC) as a cationic surfactant. Here, the retinol binding property of BLG was determined at 298 K and pH 8.0 by spectrofluorimeter titration method, in the presence of CPC to elucidate the still unknown structure-function relationship in this protein. Comparison of the results allowed determining the binding of retinol by BLG in the presence of CPC. The two-way chemometrics method was used, to estimate the equilibrium concentration of components by analysis of fluorescence emission spectrum, in order to obtain its equilibrium concentration. The results indicate that the retinol binding properties of BLG do not show significant changes in the presence of this surfactant

Interaction of β-Lactoglobulin with Resveratrol : Molecular Docking and Molecular Dynamics Simulation Studies

International audienceIn this work, the interaction of trans-resveratrol, as a natural polyphenolic compound, and Bovine β-lactoglobulin (BLG), was studied using molecular docking and molecular dynamics simulation methods. The molecular dynamics study makes an importantcontribution to understanding the effect of the binding of resveratrol on conformational changes of BLG and the stability of a protein-drug complex system in aqueous solution. Molecular docking studies revealed that the resveratrol was bound to the surface of the protein by two hydrogen bond interactions. The binding constant and free energy change, ΔG°, for the binding of resveratrol to BLG were about 6.6 × 105 mol L–1 and –33.4 kJ mol–1, respectively. Furthermore, the results of molecular dynamics simulation represented that the rmsd of unliganded BLG and BLG-resveratrol complex reached equilibration and oscillated around the average value after 600 ps simulation time. The study of the radius of gyration (Rg) revealed that BLG and BLG-resveratrol complexeswere stabilized around 1500 ps and also exhibited no conformational change. Finally, analyzing the rms fluctuations suggested that the structure of the ligand binding site remains approximately rigid during the simulation

Sonication Enhanced Removal of Nickel and Cobalt Ions from Polluted Water Using an Iron Based Sorbent

The effect of sonication time on removal efficiency of Ni2+ and Co2+ from wastewater in the presence of zero valence iron (ZVI) nanoparticles is described. The results showed that the presence of cobalt ions in the solution enhances the removal efficiency of nickel by ZVI nanoparticles to about 64% which is one of the advantages of this protocol

Photochemical deposition of silver on Fe2O3 nanotubes prepared by anodization and exploring their photoelectrochemical activity

Photochemical deposition of silver on Fe2O3 nanotubes prepared by anodization and exploring their photoelectrochemical activit

Photoelectrochemical Water Splitting and H₂ Generation Enhancement Using an Effective Surface Modification of W-Doped TiO₂ Nanotubes (WT) with Co-Deposition of Transition Metal Ions

W-doped TiO2 nanotube arrays (WT) were fabricated by in situ electrochemical anodization of titanium substrate. The results of the influence of different photo-deposited transition ions (CrxFe1−x, 0 ≤ x ≤ 1) on the surface of WT on photoelectrochemical (PEC) water splitting and H2 generation are presented. The crystallinities, structural, elemental, and absorption analysis were conducted by XRD, SEM, RAMAN, EDX, and UV–Vis absorption spectroscopy, which demonstrated anatase as the main crystalline phase of TiO2, and the existence of CrxFe1−x (nano)particles/film deposited on the surface of WT. The SEM images revealed that the deposition rate and morphology are highly related to the ratio of Cr and Fe ions. Under visible light illumination, the entire photoelectrodes showed a very good response to light with stable photocurrent density. PEC measurements revealed that the mixture of transition ions with a certain ratio of ions (Cr0.8Fe0.2–T) led to enhanced photocurrent density more than that of other modifiers due to decreasing charge recombination as well as improving the charge transfer. Moreover, PEC water splitting was conducted in an alkaline solution and the Cr0.8Fe0.2–T photoelectrode generated 0.85 mL cm−2 h−1 H2, which is over two times that of pristine WT

Photoelectrochemical Water Splitting and H2 Generation Enhancement Using an Effective Surface Modification of W-Doped TiO2 Nanotubes (WT) with Co-Deposition of Transition Metal Ions

W-doped TiO2 nanotube arrays (WT) were fabricated by in situ electrochemical anodization of titanium substrate. The results of the influence of different photo-deposited transition ions (CrxFe1&minus;x, 0 &le; x &le; 1) on the surface of WT on photoelectrochemical (PEC) water splitting and H2 generation are presented. The crystallinities, structural, elemental, and absorption analysis were conducted by XRD, SEM, RAMAN, EDX, and UV&ndash;Vis absorption spectroscopy, which demonstrated anatase as the main crystalline phase of TiO2, and the existence of CrxFe1&minus;x (nano)particles/film deposited on the surface of WT. The SEM images revealed that the deposition rate and morphology are highly related to the ratio of Cr and Fe ions. Under visible light illumination, the entire photoelectrodes showed a very good response to light with stable photocurrent density. PEC measurements revealed that the mixture of transition ions with a certain ratio of ions (Cr0.8Fe0.2&ndash;T) led to enhanced photocurrent density more than that of other modifiers due to decreasing charge recombination as well as improving the charge transfer. Moreover, PEC water splitting was conducted in an alkaline solution and the Cr0.8Fe0.2&ndash;T photoelectrode generated 0.85 mL cm&minus;2 h&minus;1 H2, which is over two times that of pristine WT

High-efficiency photoelectrochemical cathodic protection performance of the iron-nitrogen-sulfur-doped TiO(2)nanotube as new efficient photoanodes

Novel iron-nitrogen-sulfur-tridoped titanium dioxide nanotubes (Fe-N-S-TiO2NTs) have been synthesized via single step anodization of titanium using potassium ferricyanide, as a suitable additive, in dimethyl sulfoxide (DMSO) electrolyte and applied as photoanodes in the photocathodic protection of stainless steel 403 (SS403). Photocurrent density, open circuit potential and Tafel polarization curves have been used to study the photocathodic protection effect of the samples prepared. Upon the addition of potassium ferricyanide to the anodizing electrolyte and titanium dioxide nanotube doping, the light absorption of the Fe-N-S-TiO2NTs were increased to the visible region, comparable with pure TiO2NTs, according to the results obtained. Enhanced photoelectro-response activity and photocathodic protection performance for 403 stainless steel are exhibited by Fe-N-S-TiO2NTs under light illumination. In addition, the optimal sample electrode (FT4) potentials shifted negatively to -683 mV under illumination