Studies on interaction of azo dyes with bovine serum albumin, as carrier protein, would be of particular importance in the field of toxicology that can help in better understanding of dye-protein interaction mechanism. In this regard, the interaction between the azo dye, trisodium (4E)-3-oxo-4-[(4-sulfonato-1-naphthyl) hydrazono] naphthalene-2,7-disulfonate (C20H11N2Na3O10S3), known as Amaranth, and bovine serum albumin (BSA) was studied using UV-Vis absorption, fluorescence spectroscopy, viscosity measurement and molecular docking studies. Also, the association behavior of Amaranth was investigated at its various concentrations and different ionic strengths (NaCl) in 5 mM aqueous phosphate buffer of pH 7.0 at 25 °C. From the spectrophotometric studies, the binding constant was determined. The value of the binding constant was Kb = 0.71 × 104 M-1 at 298 K. Thermodynamic parameters (ΔH > 0 and ΔS > 0) indicated that hydrophobic forces play a major role in the interaction between Amaranth and BSA. From the results of fluorescent experiments, the binding constants and the number of binding sites were obtained as Kb = 3.4 × 107 M-1 and 1.2901, respectively. By increasing the amount of Amaranth, a significant increase in viscosity of BSA was observed. The molecular docking method was employed to understand the interaction of Amaranth with BSA. The results showed that BSA has great affinity for interaction with Amaranth dye.
AUTHOR KEYWORDS: Bovine serum albumin; Fluorescence quenching; Molecular docking; Thermodynamic; Toxic Azo dye PUBLISHER: Iranian Chemical Society
To investigate the interaction and adsorption of drug and carbon nanotube on human serum albumin, three anti-cancer drugs ([Pd(phen)(R-gly)]NO3, R = methyl, propyl and amyl) with different hydrophobic tails and anticancer activities were selected. These drugs have better anti-tumor activity and less side effects than that known cis-platinum drug. Human serum albumin is also important for drug delivery and release and acts as carrier of internal biological molecules and external drugs that bind to many drugs in blood route and carry them. Drug binding to human serum albumin can change its helicity and this can affect on the drug release and distribution. Thus, study of this aspect can provide structural features determining the therapeutic efficiency of drug that has the least effect on human serum albumin helix structure. Interaction of three drugs with human serum albumin was investigated by molecular dynamics simulation and the best drug with the least denaturation effect was selected to compare its effect in the presence of nanotube. The structure of protein was again compared in the presence of drug and nanotube. The results revealed less denaturation effect of methyl on human serum albumin structure. The denaturation of protein also decreased more in the presence of nanotube. Carbon nanotube can be used as a cover for denaturation effect of drug and leads to better orientation and less random movement of drug around protein. It also reveals drug interaction with protein binding site facilitated in the presence of carbon nanotube.
AUTHOR KEYWORDS: Carbon nanotube (CNT); Denaturation; Helix; Human serum albumin (HSA); Molecular dynamics simulation PUBLISHER: Iranian Chemical Society
AUTHOR KEYWORDS: carbon nanotube; flow of water; free energy; molecular dynamics simulation; orthogonal and axial electric field INDEX KEYWORDS: Electric fields; Flow of water; Free energy; Hydraulics; Molecular dynamics; Molecules; Nanotubes; Yarn, Electric field strength; Electric-field directions; Molecular dynamics simulations; Orthogonal electric fields; Reverse behavior; Water molecule; Water permeation; Water transportation, Carbon nanotubes PUBLISHER: Maik Nauka-Interperiodica Publishing
AUTHOR KEYWORDS: Drug delivery; Encapsulation; Molecular dynamics simulation; Multiple linear regressions; Radius of gyration INDEX KEYWORDS: Aromatic compounds; Carbon; Drug delivery; Drug interactions; Encapsulation; Free energy; Molecular dynamics; Molecules; Regression analysis; Yarn, Free energy of interactions; Free-energy calculations; Molecular dynamics simulations; Multiple linear regressions; Potential of mean force; Quantitative structure property relationships; Radius of gyration; Regression parameters, Carbon nanotubes PUBLISHER: Korean Chemical Society
Molecular dynamics simulations at 270 and 310 K rationalized the effect of urea, temperature and the size of the carbon nanotube, on the insertion of Tretinoin into nanotubes with chirality (10, 7) and (8, 5). Concentrations of 0.9 mmol L-1 and 2 mol L-1 of urea are studied, that are less and more than the normal range of blood urea content, respectively. Results show that encapsulation of Tretinoin could be ascribed to the flow of the waters via hydrophilic and van der Waals interactions and diameter of the nanotube. Heat capacity, diffusion coefficient, free energy and contact coefficient change with the temperature and urea. Tretinoin molecule locates inside the nanotube due to the partial ππ interactions between oxygen atom of Tretinoin and the conjugated aromatic rings of nanotube. Finally, high concentration of urea causes the striking phenomenon of inducing the drying of nanotube that result in urea wires and instability of encapsulation.
AUTHOR KEYWORDS: Carbon nanotube; Linear interaction energy; Molecular dynamics simulation; Tretinoin PUBLISHER: Sociedade Brasileira de Quimica
Co(II)-tetrasulfonated phthalocyanine (CoTSP) is known to be aggregated to dimer at high concentration levels in water. A study on the aggregation of CoTSP using multivariate curve resolution analysis of the visible absorbance spectra over a concentration range of 30, 40 and 50 μM in the presence of dimethyl sulfoxide (DMSO), dimethyl formamide (DMF), acetonitrile (AN) and ethanol (EtOH) in the concentration range of 0 to 3.57 M is conducted. A hard modeling-based multivariate curve resolution method was applied to determine the dissociation constants of the CoTSP aggregates at various temperatures ranging from 25, 45 and 65 °C and in the presence of various co-solvents. Dissociation constant for aggregation was increased and then decrease by temperature and concentration of phthalocyanine, respectively. Utilizing the vant Hoff relation, the enthalpy and entropy of the dissociation equilibriums were calculated. For the dissociation of both aggregates, the enthalpy and entropy changes were positive and negative, respectively. Molecular dynamics simulation of cosolvent effect on CoTSP aggregation was done to confirm spectroscopy results. Results of radial distribution function (RDF), root mean square deviation (RMSD) and distance curves confirmed more effect of polar solvent to decrease monomer formation.
AUTHOR KEYWORDS: Molecular dynamics simulation; Multivariate curve resolution; Phthalocyanine; Solvent effect; Spectroscopy INDEX KEYWORDS: Dimers; Dimethyl sulfoxide; Dissociation; Enthalpy; Entropy; Molecular dynamics; Nitrogen compounds; Organic solvents; Phase equilibria; Solvents; Spectroscopy, Molecular dynamics calculation; Molecular dynamics simulations; Multivariate curve resolution; Multivariate curve resolution analysis; Phthalocyanine; Radial distribution functions; Root mean square deviations; Solvent effects, Aggregates PUBLISHER: Korean Chemical Society
Molecular dynamic simulation is a powerful method that monitors all variations in the atomic level in explicit solvent. By this method we can calculate many chemical and biochemical properties of large scale biological systems. In this work, all-atom molecular dynamic simulation of polyalanine (PA) was investigated in the presence of 0.224, 0.448, 0.673, 0.897 and 1.122 M of guanidinium chloride (GdmCl) at 273-395 K by molecular dynamics simulation. Analysis of surface area, radial distribution function, radius of gyration, heat capacity, hydrogen bond, helix, coil and beta contents showed that an intermediate appears on the way of helix to coil transition. GdmCl at low concentration increases the midpoint of transition temperature (Tm), number of solvent molecules in the hydration layer and interapeptide hydrogen bond as well as decreases in rate of helix to coil transition. Thus, the role of guanidine at low concentration is as the same as osmolytes which decreases the beta form and, increases hydration layer and the polypeptide thermal stability.
AUTHOR KEYWORDS: Heat capacity; Intermediate; Phase transition; Polyalanine; Thermal stability PUBLISHER: Iranian Chemical Society
Due to increasing of population of diabetic patients, identifying factors for disease control has received much attention, α-glucosidase (EC 188.8.131.52) is an essential enzyme that helps to digestion of carbohydrates such as starch and sugar. Carbohydrates are normally converted into simple sugars, which can be absorbed through the intestine. Therefore, α-glucosidase inhibitors can be used to decrease the blood sugar level. We have studied the effect of inhibition of N-(phe-noxydecyl) phthalimide derivatives by a computer drug-design protocol involving homology modeling, docking simulation and Quantitative Structure Activity Relationship. The homology modeling of a-glucosidase showed a structure very similar to the crystal structure of oligo-l,6-glucosidase from Saccharomyces cerevisiae. Docking results showed the position of inhibitors binding site is close to active site and the carboxyl oxygen in phthalimide is an effective functional group for binding inhibitors to protein. The equation obtained by QS AR showed that, logIC 50 decreases and so inhibition property increases when the size, polarity, geometry and number of halogen factors increase.
Kinetic and structural studies have been carried out on the effects of meso-tetrakis(4-sulfonatophenyl)- porphyrin (H2TPPS4) as an anionic and meso-tetrakis(3-N-methyl-pyridyl)porphyrin (H2TMPYP) as a cationic porphyrin with adenosine deaminase (ADA) in 25 mM citrate/phosphate buffer, pH = 4-8, at 37 °C using UVvis spectrophotometry, circular dichroism (CD), fluorescence spectrophotometry as well as molecular dynamics (MD) and molecular docking. Kinetic results showed that the two porphyrins are non-competitive inhibitors. Increasing pH, increases KI and cationic porphyrin has a higher KI and lower binding constant (Kb) at all pH ranges. Analyzing the secondary structure revealed that both ligands decrease the secondary structure and that the anionic porphyrin is more effective.
Effects of some diacid, diamine and dinitro aromatic compounds on the structure and activity of adenosine deaminase (ADA) were investigated by UV-Vis spectrophotometry in 50 mM phosphate buffer at pH = 7.5 and 27°C and molecular docking studies. The results showed that all tested ligands are showing inhibition; five ligands are uncompetitive and other two ligands are mixed of competitive and noncompetetive inhibitors with majority of competitive behavior. For the later case analysis was done based on competitive inhibition. Diacids have larger size and higher inhibition constant (KI) relative to others. A logical correlation between calculated free energy of binding and experimental values was obtained for un-competitive. Experimental and calculated data showed that competitive inhibitors are distributed near the active site of enzyme and form several cluster of ranks, whereas uncompetitive inhibitors bind to the enzyme-substrate complex and distributed far from the active site. Results of structure-activity relationship showed that, larger, more hydrophobe, less spherical and more aromatic ligands have higher inhibition constants.
AUTHOR KEYWORDS: Binding constant; Enzyme inhibition; Principal component analysis; QSAR INDEX KEYWORDS: Active site; Adenosine deaminases; Aromatic ligands; Binding constant; Case analysis; Competitive behavior; Competitive inhibition; Dinitro aromatic compounds; Enzyme-substrate complexes; Experimental values; Free energy of binding; Inhibition constants; Molecular docking; Phosphate buffers; QSAR studies; Structure activity relationships; UV-vis spectrophotometry, Aromatic compounds; Binding energy; Docking; Enzymes; Financial data processing; Ligands; Molecular modeling; pH effects; Principal component analysis; Sulfur compounds, Enzyme inhibition
The relationship between thermal decomposition temperature and structure of a new data set of eighty monomers of different polymers were studied by multiple linear regression (MLR). The stepwise method was used in order to variable selection. The best descriptors were selected from over 1400 descriptors including; topological, geometrical, electronic and hybrid descriptors. The effect of number of descriptors on the correlation coefficient (R) and F-ratio were considered. Two models were suggested, one model having four descriptors (R2 = 0.894, Q2 cv = 0.900, F = 172.1) and other model involving 13 descriptors (R2 = 0.956, Q 2 cv = 0.956, F = 125.4).
AUTHOR KEYWORDS: Cross validation; Geometrical descriptors; Polymer; Semi-empirical; Thermal decomposition temperature INDEX KEYWORDS: Decomposition; Linear regression; Thermolysis, Correlation coefficient; Cross validation; Descriptors; Multiple linear regressions; Semi-empirical; Stepwise methods; Thermal decomposition temperature; Variable selection, Polymers PUBLISHER: Korean Chemical Society
The kinetic and thermodynamic effects of aspirin and diclofenac on the activity of adenosine deaminase (ADA) were studied in 50 mM phosphate buffer pH = 7.5 at 27 and 37°C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 37°C and the inhibition constants are 42.8 and 96.8μM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 27°C and uncompetitive at 37°C with inhibition constants of 56.4 and 30.0 μM, at respectively. The binding constant and enthalpy of binding, at 27°C are 45 μM, -64.5kJ/mol and 61 μM, - 34.5 kJ/mol for aspirin and diclofenac. Thermodynamic data revealed that the binding process for these ADA inhibitors is enthalpy driven. QSAR studies by principal component analysis implemented in SPSS show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constants.
The interaction of a polyoxometal (POM), K6SiW 11Co(H2O)O39.10H2O (K6) as a Keggin, with human serum albumin (HSA) was studied by different methods and techniques. Binding studies show two sets of binding sites for interaction of POM to HSA. Binding analysis and isothermal calorimetery revealed that, the first set of binding site has lower number of bound ligand per mole of protein ( ν), lower Hill constant (n), higher binding constant (K), more negative entropy (ΔS) and more electrostatic interaction in comparison to the second set of binding site. In addition, differential scanning calorimetery (DSC) and spectrophotometery data showed that, there are two energetic domains. The first domain is less stable (lower Tm and Cp) which corresponds to the tail segment of HSA and another with more stability is related to the head segment of HSA. Polyoxometal also decreases the stability of protein as Tm, secondary and tertiary structure as well as quenching of the fluorescence decrease. On other hand, perturbations in tertiary structure are more than secondary structure.
AUTHOR KEYWORDS: Circular dichroism; Fluorescence; Human serum albumin; Isothermal titration calorimetery; Polyoxometalate INDEX KEYWORDS: Blood; Coulomb interactions; Differential scanning calorimetry; Fluorescence; Molecular structure; Perturbation techniques; Thermodynamics, Circular dichroisms; Human serum albumin (HSA); Isothermal titration calorimetery; Polyoxometalate, Proteins PUBLISHER: Korean Chemical Society
The kinetic parameters of adenosine deaminase such as Km and Ki were determined in the absence and presence of adenine derivatives (R1- R24) in sodium phosphate buffer (50 mM; pH 7.5) solution at 27°C. These kinetic parameters were used for QSAR analysis. As such, we found some theoretical descriptors to which the binding affinity of adenosine deaminase (ADA) towards several adenine nucleosides as inhibitors is correlated. QSAR analysis has revealed that binding affinity of the adenine nucleosides upon interaction with ADA depends on the molecular volume, dipole moment of the molecule, electric charge around the N1 atom, and the highest of positive charge for the related molecules.
The stability of four hemoglobins (Hb) in dimer forms (low concentration) were investigated by the kinetics of denaturation. The rate constants of denaturation were obtained by variation of 280 nm absorption versus time in 10 mM Tris-HCl, 10 mM EDTA, pH 8.0 at 45°C in the absence and presence of 0.5 M ethanol, dimethyl sulfoxide (DMSO), formamide, and glycerol. The results show the trend of rate constants in different co-solvents in the following order: chicken hemolysate < human hemolysate and chicken Hb D < chicken Hb A. The buried surface area was calculated for Hb samples in the absence of co-solvents. Accordingly, the trend points out that: chicken Hb D > chicken Hb A > human Hb A. These results suggest that both chicken hemolysate and chicken Hb D are relatively more stable than human and chicken Hb A, respectively. However, the denaturation rate constants of Hb in different co-solvents have designated the following order: ethanol > DMSO > formamide > glycerol. As a matter of fact, this phenomenon is an indication of an increase in the denaturation capacity (DC) and hydrophobicity, and a decrease in the surface tension of the solution in the preceding co-solvents.
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