Combined spectroscopies and molecular docking approach to characterizing the binding interaction of enalapril with bovine serum albumin

The binding interaction between bovine serum albumin (BSA) and enalapril (ENPL) at the imitated physiological conditions (pH = 7.4) was investigated using UV–vis absorption spectroscopy (UV–vis), fluorescence emission spectroscopy (FES), synchronous fluorescence spectroscopy (SFS), Fourier transform infrared spectroscopy (FT‐IR), circular dichroism (CD) and molecular docking methods. It can be deduced from the experimental results from the steady‐state fluorescence spectroscopic titration that the intrinsic BSA fluorescence quenching mechanism induced by ENPL is static quenching, based on the decrease in the BSA quenching constants in the presence of ENPL with increase in temperature and BSA quenching rates >10¹⁰ L mol^?1 sec^?1. This result indicates that the ENPL–BSA complex is formed through an intermolecular interaction of ENPL with BSA. The main bonding forces for interaction of BSA and ENPL are van der Waal's forces and hydrogen bonding interaction based on negative values of Gibbs free energy change (ΔG ⁰), enthalpic change (ΔH ⁰) and entropic change (ΔS ⁰). The binding of ENPL with BSA is an enthalpy‐driven process due to |ΔH °| > |T ΔS °| in the binding process. The results of competitive binding experiments and molecular docking confirm that ENPL binds in BSA sub‐domain IIA (site I) and results in a slight change in BSA conformation, but BSA still retains its α‐helical secondary structure.     

Intermolecular interaction of fosinopril with bovine serum albumin (BSA): The multi‐spectroscopic and computational investigation

The intermolecular interaction of fosinopril, an angiotensin converting enzyme inhibitor with bovine serum albumin (BSA), has been investigated in physiological buffer (pH 7.4) by multi‐spectroscopic methods and molecular docking technique. The results obtained from fluorescence and UV absorption spectroscopy revealed that the fluorescence quenching mechanism of BSA induced by fosinopril was mediated by the combined dynamic and static quenching, and the static quenching was dominant in this system. The binding constant, K_b, value was found to lie between 2.69 × 10³ and 9.55 × 10³ M^?1 at experimental temperatures (293, 298, 303, and 308 K), implying the low or intermediate binding affinity between fosinopril and BSA. Competitive binding experiments with site markers (phenylbutazone and diazepam) suggested that fosinopril preferentially bound to the site I in sub‐domain IIA on BSA, as evidenced by molecular docking analysis. The negative sign for enthalpy change (ΔH⁰) and entropy change (ΔS⁰) indicated that van der Waals force and hydrogen bonds played important roles in the fosinopril‐BSA interaction, and 8‐anilino‐1‐naphthalenesulfonate binding assay experiments offered evidence of the involvements of hydrophobic interactions. Moreover, spectroscopic results (synchronous fluorescence, 3‐dimensional fluorescence, and Fourier transform infrared spectroscopy) indicated a slight conformational change in BSA upon fosinopril interaction.     

Spectroscopic and molecular docking studies on the interaction between N‐acetyl cysteine and bovine serum albumin

The interaction between N‐acetyl cysteine (NAC) and bovine serum albumin (BSA) was investigated by UV–vis, fluorescence spectroscopy, and molecular docking methods. Fluorescence study at three different temperatures indicated that the fluorescence intensity of BSA was reduced upon the addition of NAC by the static quenching mechanism. Binding constant (K_b) and the number of binding sites (n) were determined. The binding constant for the interaction of NAC and BSA was in the order of 10³ M^?1, and the number of binding sites was obtained to be equal to 1. Enthalpy (ΔH), entropy (ΔS), and Gibb's free energy (ΔG) as thermodynamic values were also achieved by van't Hoff equation. Hydrogen bonding and van der Waals force were the major intermolecular forces in the interaction process and it was spontaneous. Finally, the binding mode and the binding sites were clarified using molecular docking which were in good agreement with the results of spectroscopy experiments. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 638–645, 2015.     

Study on the interaction between anti‐tuberculosis drug ethambutol and bovine serum albumin: multispectroscopic and cyclic voltammetric approaches

The binding of bovine serum albumin (BSA) to ethambutol (EMB) was investigated using spectroscopic methods, viz., fluorescence, Fourier transform infrared (FTIR), ultraviolet (UV)/vis absorption and cyclic voltammetry techniques. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of serum albumin by EMB is static, which was also confirmed by lifetime measurements. The number of binding sites, n, and binding constant, K, were obtained at various temperatures. The distance, r, between EMB and the protein was evaluated according to the Förster energy transfer theory. Based on displacement experiments using site probes, viz., warfarin, ibuprofen and digitoxin, the site of binding of EMB in BSA was proposed to be Sudlow's site I. The effect of EMB on the conformation of BSA was analyzed by using synchronous fluorescence spectra (SFS) and 3D fluorescence spectra. The results of fluorescence, UV/vis absorption and FTIR spectra showed that the conformation of BSA was changed in the presence of EMB. The thermodynamic parameters including enthalpy change (ΔH⁰), entropy change (ΔS⁰) and free energy change (ΔG⁰) for BSA–EMB were calculated according to the van't Hoff equation and are discussed.     

Probing the behavior of bovine serum albumin upon binding to atenolol: insights from spectroscopic and molecular docking approaches

Molecular interaction of atenolol, a selective β₁ receptor antagonist with the major carrier protein, bovine serum albumin (BSA), was investigated under imitated physiological conditions (pH 7.4) by means of fluorescence spectroscopy, UV absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and molecular modeling studies. The steady-state fluorescence spectra manifested that static type, due to formation of the atenolol-BSA complex, was the dominant mechanism for fluorescence quenching. The characteristic information about the binding interaction of atenolol with BSA in terms of binding constant (K_b) were determined by the UV–vis absorption titration, and were found to be in the order of 10³ M^?1 at different temperatures, indicating the existence of a weak binding in this system. Thermodynamic analysis revealed that the binding process was primarily mediated by van der Waals force and hydrogen bonds due to the negative sign for enthalpy change (ΔH⁰), entropy change (ΔS⁰). The molecular docking results elucidated that atenolol preferred binding on the site II of BSA according to the findings observed in competitive binding experiments. Moreover, via alterations in synchronous fluorescence, three-dimensional fluorescence and FT-IR spectral properties, it was concluded that atenolol could arouse slight configurational and micro-environmental changes of BSA.     

Fluorescent bovine serum albumin interacting with the antitussive quencher dextromethorphan: a spectroscopic insight

The interaction of dextromethorphan hydrobromide (DXM) with bovine serum albumin (BSA) is studied by using fluorescence spectra, UV–vis absorption, synchronous fluorescence spectra (SFS), 3D fluorescence spectra, Fourier transform infrared (FTIR) spectroscopy and circular dichroism under simulated physiological conditions. DXM effectively quenched the intrinsic fluorescence of BSA. Values of the binding constant, K_A, are 7.159 × 10³, 9.398 × 10³ and 16.101 × 10³ L/mol; the number of binding sites, n, and the corresponding thermodynamic parameters ΔG°, ΔH° and ΔS° between DXM and BSA were calculated at different temperatures. The interaction between DXM and BSA occurs through dynamic quenching and the effect of DXM on the conformation of BSA was analyzed using SFS. The average binding distance, r, between the donor (BSA) and acceptor (DXM) was determined based on Förster's theory. The results of fluorescence spectra, UV–vis absorption spectra and SFS show that the secondary structure of the protein has been changed in the presence of DXM. Copyright © 2015 John Wiley & Sons, Ltd.     

Investigations on the interactions of DiAmsar with serum albumins: Insights from spectroscopic and molecular docking techniques

Diamine‐sarcophagine (DiAmsar) binding to human serum albumin (HSA) and bovine serum albumin (BSA) was investigated under simulative physiological conditions. Fluorescence spectra in combination with Fourier transform infrared (FT‐IR), UV‐visible (UV–vis) spectroscopy, cyclic voltammetry (CV), and molecular docking method were used in the present work. Experimental results revealed that DiAmsar had an ability to quench the HSA and BSA intrinsic fluorescence through a static quenching mechanism. The Stern–Volmer quenching rate constant (K_sv) was calculated as 0.372 × 10³ M^‐1 and 0.640 × 10³ M^‐1 for HSA and BSA, respectively. Moreover, binding constants (K_a), number of binding sites (n) at different temperatures, binding distance (r), and thermodynamic parameters (?H°, ?S°, and ?G°) between DiAmsar and HSA (or BSA) were calculated. DiAmsar exhibited good binding propensity to HSA and BSA with relatively high binding constant values. The positive ?H° and ?S° values indicated that the hydrophobic interaction is main force in the binding of the DiAmsar to HSA (or BSA). Furthermore, molecular docking results revealed the possible binding site and the microenvironment around the bond. Copyright © 2014 John Wiley & Sons, Ltd.     

Study on the interaction between pelargonidin‐3‐O‐glucoside and bovine serum albumin using spectroscopic,transmission electron microscopy and molecular modeling techniques

The aim of this study is to evaluate the binding behavior between pelargonidin‐3‐O‐glucoside (P3G) and bovine serum albumin (BSA) using multi‐spectroscopic, transmission electron microscopy (TEM) and molecular docking methods under physiological conditions. Fluorescence spectroscopy and time‐resolved fluorescence showed that the fluorescence of BSA could be quenched remarkably by P3G via a static quenching mechanism, and there is a single class of binding site on BSA. In addition, the thermodynamic functions ΔH and ΔS were –21.69 kJ/mol and 24.46 J/mol/K, indicating that an electrostatic interaction was a main acting force. The distance between BSA and P3G was 2.74 nm according to Förster's theory, illustrating that energy transfer occurred. In addition, the secondary structure of BSA changed with a decrease in the α‐helix content from 66.2% to 64.0% as seen using synchronous fluorescence, UV/vis, circular dichroism and Fourier transform infrared spectroscopies, whereas TEM images showed that P3G led to BSA aggregation and fibrillation. Furthermore, site marker competitive experiments and molecular docking indicated that P3G could bind with subdomain IIA of BSA. The calculated results of the equilibrium fraction showed that the concentration of free P3G in plasma was high enough to be stored and transported from the circulatory system to its target sites to provide therapeutic effects. Copyright © 2015 John Wiley & Sons, Ltd.     

Multispectroscopic exploration and molecular docking analysis on interaction of eriocitrin with bovine serum albumin

Eriocitrin is a flavanone glycoside, which exists in lemon or lime citrus fruits. It possesses antioxidant, anticancer, and anti‐allergy activities. In order to investigate the pharmacokinetics and pharmacological mechanisms of eriocitrin in vivo, the interaction between eriocitrin and bovine serum albumin (BSA) was studied under the simulated physiological conditions by multispectroscopic and molecular docking methods. The results well indicated that eriocitrin and BSA formed a new eriocitrin‐BSA complex because of intermolecular interactions, which was demonstrated by the results of ultraviolet‐visible (UV‐vis) absorption spectra. The intrinsic fluorescence of BSA was quenched by eriocitrin, and static quenching was the quenching mechanism. The number of binding sites (n) and binding constant (K_b) at 310 K were 1.22 and 2.84 × 10⁶ L mol^?1, respectively. The values of thermodynamic parameters revealed that the binding process was spontaneous, and the main forces were the hydrophobic interaction. The binding distance between eriocitrin and BSA was 3.43 nm. In addition, eriocitrin changed the conformation of BSA, which was proved by synchronous fluorescence and circular dichroism (CD) spectra. The results of site marker competitive experiments suggested that eriocitrin was more likely to be inserted into the subdomain IIA (site I), which was further certified by molecular docking studies.     

Characterization of interactions of simvastatin,pravastatin, fluvastatin,and pitavastatin with bovine serum albumin: multiple spectroscopic and molecular docking

The binding interactions of simvastatin (SIM), pravastatin (PRA), fluvastatin (FLU), and pitavastatin (PIT) with bovine serum albumin (BSA) were investigated for determining the affinity of four statins with BSA through multiple spectroscopic and molecular docking methods. The experimental results showed that SIM, PRA, FLU, and PIT statins quenched the intrinsic fluorescence of BSA through a static quenching process and the stable stains–BSA complexes with the binding constants in the order of 10⁴ M^?1 at 298 K were formed through intermolecular nonbond interaction. The values of ΔH⁰, ΔS⁰ and ΔG⁰ in the binding process of SIM, PRA, FLU, and PIT with BSA were negative at the studied temperature range, suggesting that the binding process of four statins and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen-bonding interactions. Moreover, the binding of four statins with BSA was enthalpy-driven process due to |ΔH°|>|TΔS°| under the studied temperature range. From the results of site marker competitive experiments and molecular docking, subdomain IIIA (site II) was the primary binding site for SIM, PRA, FLU, and PIT on BSA. The results of UV–vis absorption, synchronous fluorescence, 3D fluorescence and FT-IR spectra proved that the slight change in the conformation of BSA, while the significant changes in the conformation of SIM, PRA, FLU, and PIT drug in statin–BSA complexes, indicating that the flexibility of statin molecules plays an important role in increasing the stability of statin–BSA complexes.     

Study of the interaction between sodium salts of (2E)‐3‐(4'‐halophenyl)prop‐2‐enoyl sulfachloropyrazine and bovine serum albumin by fluorescence spectroscopy

Three sodium salts of (2E)‐3‐(4'‐halophenyl)prop‐2‐enoyl sulfachloropyrazine (CCSCP) were synthesized and their structures were determined by ¹H and ¹³C NMR, LC‐MS and IR. The binding properties between CCSCPs and bovine serum albumin (BSA) were studied using fluorescence spectroscopy in combination with UV–vis absorbance spectroscopy. The results indicate that the fluorescence quenching mechanisms between BSA and CCSCPs were static quenching at low concentrations of CCSCPs or combined quenching (static and dynamic) at higher CCSCP concentrations of 298, 303 and 308 K. The binding constants, binding sites and corresponding thermodynamic parameters (ΔH, ΔS, ΔG) were calculated at different temperatures. All ΔG values were negative, which revealed that the binding processes were spontaneous. Although all CCSCPs had negative ΔH and positive ΔS, the contributions of ΔH and ΔS to ΔG values were different. When the 4'‐substituent was fluorine or chlorine, van der Waals interactions and hydrogen bonds were the main interaction forces. However, when the halogen was bromine, ionic interaction and proton transfer controlled the overall energetics. The binding distances between CCSCPs and BSA were determined using the Förster non‐radiation energy transfer theory and the effects of CCSCPs on the conformation of BSA were analyzed by synchronous fluorescence spectroscopy. Copyright © 2012 John Wiley & Sons, Ltd.     

Exploration of interaction of canthaxanthin with human serum albumin by spectroscopic and molecular simulation methods

The interaction between the food colorant canthaxanthin (CA) and human serum albumin (HSA) in aqueous solution was explored by using fluorescence spectroscopy, three‐dimensional fluorescence spectra, synchronous fluorescence spectra, UV–vis absorbance spectroscopy, circular dichroism (CD) spectra and molecular docking methods. The thermodynamic parameters calculated from fluorescence spectra data showed that CA could result in the HSA fluorescence quenching. From the K_SV change with the temperature dependence, it was concluded that HSA fluorescence quenching triggered by CA is the static quenching and the number of binding sites is one. Furthermore, the secondary structure of HSA was changed with the addition of CA based on the results of synchronous fluorescence, three‐dimensional fluorescence and CD spectra. Hydrogen bonds and van der Waals forces played key roles in the binding process of CA with HSA, which can be obtained from negative standard enthalpy (ΔH) and negative standard entropy (ΔS). Furthermore, the conclusions were certified by molecular docking studies and the binding mode was further analyzed with Discovery Studio. These conclusions can highlight the potential of the interaction mechanism of food additives and HSA.     

Characterization of intermolecular interaction between cyanidin‐3‐glucoside and bovine serum albumin: Spectroscopic and molecular docking methods

The intermolecular interaction between cyanidin‐3‐glucoside (Cy‐3‐G) and bovine serum albumin (BSA) was investigated using fluorescence, circular dichroism and molecular docking methods. The experimental results revealed that the fluorescence quenching of BSA at 338 nm by Cy‐3‐G resulted from the formation of Cy‐3‐G–BSA complex. The number of binding sites (n) for Cy‐3‐G binding on BSA was approximately equal to 1. The experimental and molecular docking results revealed that after binding Cy‐3‐G to BSA, Cy‐3‐G is closer to the Tyr residue than the Trp residue, the secondary structure of BSA almost not change, the binding process of Cy‐3‐G with BSA is spontaneous, and Cy‐3‐G can be inserted into the hydrophobic cavity of BSA (site II′) in the binding process of Cy‐3‐G with BSA. Moreover, based on the sign and magnitude of the enthalpy and entropy changes (ΔH⁰ = – 29.64 kcal/mol and ΔS⁰ = – 69.51 cal/mol K) and the molecular docking results, it can be suggested that the main interaction forces of Cy‐3‐G with BSA are Van der Waals and hydrogen bonding interactions. Copyright © 2013 John Wiley & Sons, Ltd.     

Molecular docking and experimental investigation of new indole derivative cyclooxygenase inhibitor to probe its binding mechanism with bovine serum albumin

The indole derivative 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene]acetohydrazide (IND) was synthesized for its therapeutic potential to inhibit cyclooxygenase (COX)-II. Binding if IND to bovine serum albumin (BSA) was investigated was because most drugs bind to serum albumin in-vivo. Fluorescence, UV–vis spectrophotometry and molecular modeling methodologies were employed for studying the interaction mechanism. The intrinsic fluorescence of BSA was quenched by BSA and the quenching mechanism involved was static quenching. The binding constants between IND and BSA at the three studied temperatures (298, 301 and 306 K) were 1.09 × 10⁵, 4.36 × 10⁴ and 1.23 × 10⁴ L mol⁻¹ respectively. The most likely site for binding IND to BSA was Site I (subdomain IIA). The analysis of thermodynamic parameter revealed the involvement of hydrogen bonding and van der Waals forces in the IND-BSA interaction. Synchronous fluorescence spectroscopic (SFS) and UV–vis spectrophotometric studies suggested conformational change in BSA molecule post interaction to IND. Molecular docking and the experimental results corroborated one another. The study can prove as an insight for future IND drug development.     

In vitro study on binding interaction of quinapril with bovine serum albumin (BSA) using multi-spectroscopic and molecular docking methods

The binding interaction between quinapril (QNPL) and bovine serum albumin (BSA) in vitro has been investigated using UV absorption spectroscopy, steady-state fluorescence spectroscopic, synchronous fluorescence spectroscopy, 3D fluorescence spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, and molecular docking methods for obtaining the binding information of QNPL with BSA. The experimental results confirm that the quenching mechanism of the intrinsic fluorescence of BSA induced by QNPL is static quenching based on the decrease in the quenching constants of BSA in the presence of QNPL with the increase in temperature and the quenching rates of BSA larger than 10¹⁰ L mol^?1 s^?1, indicating forming QNPL–BSA complex through the intermolecular binding interaction. The binding constant for the QNPL–BSA complex is in the order of 10⁵ M^?1, indicating there is stronger binding interaction of QNPL with BSA. The analysis of thermodynamic parameters together with molecular docking study reveal that the main binding forces in the binding process of QNPL with BSA are van der Waal’s forces and hydrogen bonding interaction. And, the binding interaction of BSA with QNPL is an enthalpy-driven process. Based on Förster resonance energy transfer, the binding distance between QNPL and BSA is calculated to be 2.76 nm. The results of the competitive binding experiments and molecular docking confirm that QNPL binds to sub-domain IIA (site I) of BSA. It is confirmed there is a slight change in the conformation of BSA after binding QNPL, but BSA still retains its secondary structure α-helicity.     

Binding of fluphenazine with human serum albumin in the presence of rutin and quercetin: An evaluation of food‐drug interaction by spectroscopic techniques

The interactions between human serum albumin (HSA) and fluphenazine (FPZ) in the presence or absence of rutin or quercetin were studied by fluorescence, absorption and circular dichroism (CD) spectroscopy and molecular modeling. The results showed that the fluorescence quenching mechanism was static quenching by the formation of an HSA–FPZ complex. Entropy change (ΔS ⁰) and enthalpy change (ΔH ⁰) values were 68.42 J/(mol? K) and ?4.637 kJ/mol, respectively, which indicated that hydrophobic interactions and hydrogen bonds played major roles in the acting forces. The interaction process was spontaneous because the Gibbs free energy change (ΔG ⁰) values were negative. The results of competitive experiments demonstrated that FPZ was mainly located within HSA site I (sub‐domain IIA). Molecular docking results were in agreement with the experimental conclusions of the thermodynamic parameters and competition experiments. Competitive binding to HSA between flavonoids and FPZ decreased the association constants and increased the binding distances of FPZ binding to HSA. The results of absorption, synchronous fluorescence, three‐dimensional fluorescence, and CD spectra showed that the binding of FPZ to HSA caused conformational changes in HSA and simultaneous effects of FPZ and flavonoids induced further HSA conformational changes.     

Study of fluorescence interaction and conformational changes of bovine serum albumin with histamine H1‐receptor–drug epinastine hydrochloride by spectroscopic and time‐resolved fluorescence methods

The fluorescence, ultraviolet (UV) absorption, time resolved techniques, circular dichroism (CD), and infrared spectral methods were explored as tools to investigate the interaction between histamine H₁ drug, epinastine hydrochloride (EPN), and bovine serum albumin (BSA) under simulated physiological conditions. The experimental results showed that the quenching of the BSA by EPN was static quenching mechanism and also confirmed by lifetime measurements. The value of n close to unity indicated that one molecule of EPN was bound to protein molecule. The binding constants (K) at three different temperatures were calculated (7.1 × 10⁴, 5.5 × 10⁴, and 3.9 × 10⁴M⁻¹). Based on the thermodynamic parameters (ΔH⁰, ΔG⁰, and ΔS⁰), the nature of binding forces operating between drug and protein was proposed. The site of binding of EPN in the protein was proposed to be Sudlow's site I based on displacement experiments using site markers viz, warfarin, ibuprofen, and digitoxin. Based on the Förster's theory of non‐radiation energy transfer, the binding average distance, r between the donor (BSA) and acceptor (EPN) was evaluated and found to be 4.48 nm. The UV–visible, synchronous fluorescence, CD, and three‐dimensional fluorescence spectral results revealed the changes in secondary structure of the protein upon its interaction with EPN. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 646–657, 2015.     

Interaction of coumarin triazole analogs to serum albumins: Spectroscopic analysis and molecular docking studies

The interaction of triazole substituted 4‐methyl‐7‐hydroxycoumarin derivatives (CUM1‐4) with serum albumin (bovine serum albumin [BSA] and human serum albumin [HSA]) have been studied employing ultraviolet‐visible (UV‐Vis), fluorescence, circular dichroism (CD) spectroscopy, and molecular docking methods at physiological pH 7.4. The fluorescence quenching occurred with increasing concentration of CUMs, and the binding constant of CUM derivatives with BSA and HSA obtained from fluorescence quenching experiment was found to be ~ 10⁴ L mol^?1. CD study showed conformational changes in the secondary structure of serum albumin upon titration of CUMs. The observed experimental results were further validated by theoretical studies involving density functional theory (DFT) and molecular docking.     

Synthesis and DNA‐binding study of imidazole linked thiazolidinone derivatives

A novel series of imidazole‐linked thiazolidinone hybrid molecules were designed and synthesized through a feasible synthetic protocol. The molecules were characterized with Fourier transform infrared (FT‐IR), ¹H nuclear magnetic resonance (NMR), ¹³C NMR and high‐resolution mass spectrometry (HRMS) techniques. In vitro susceptibility tests against Gram‐positive (S. aureus and B. subtilis ) and Gram‐negative bacteria (E. coli and P. aeruginosa ) gave highly promising results. The most active molecule (3e) gave a minimal inhibitory concentration (MIC) value of 3.125 μg/mL which is on par with the reference drug streptomycin. Structure–activity relationships revealed activity enhancement by nitro and chloro groups when they occupied meta position of the arylidene ring in 2‐((3‐(imidazol‐1‐yl)propyl)amino)‐5‐benzylidenethiazolidin‐4‐ones. DNA‐binding study of the most potent molecule 3e with salmon milt DNA (sm‐DNA) under simulated physiological pH was probed with UV–visible absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that compound 3e has a strong affinity towards DNA and binds at DNA minor groove with a binding constant (K_b) 0.18 × 10² L mol^?1. Molecular docking simulations predicted strong affinity of 3e towards DNA with a binding affinity (ΔG) ‐8.5 kcal/mol. Van der Waals forces, hydrogen bonding and hydrophobic interactions were predicted as the main forces of interaction. The molecule 3e exhibited specific affinity towards adenine–thiamine base pairs. Copyright © 2016 John Wiley & Sons, Ltd.     

Underlying molecular interaction of bovine serum albumin and linezolid: a biophysical outlook

Linezolid, one of the reserve antibiotic of oxazolidinone class has wide range of antimicrobial activity. Here we have conducted a fundamental study concerning the dynamics of its interaction with bovine serum albumin (BSA), and the post binding modification of the later by employing different spectroscopic (absorption, fluorescence and circular dichroism (CD) spectroscopy) and molecular docking tools. Gradual quenching of the tryptophan (Trp) fluorescence upon addition of linezolid to BSA confirms their interaction. Analysis of fluorescence quenching at different temperature indicates that the interaction is made by static complex formation and the BSA has one binding site for the drug. The negative Gibbs energy change (ΔG⁰), and positive values of enthalpy change (ΔH⁰) and entropy change (ΔS⁰) strongly suggest that it is an entropy driven spontaneous and endothermic reaction. The reaction involves hydrophobic pocket of the protein, which is further stabilized by hydrogen bonding and electrostatic interactions as evidenced from 8-anilino-1-napthalene sulfonic acid, sucrose and NaCl binding studies. These findings also support the molecular docking study using AutoDock 4.2. The influence of this interaction on the secondary structure of the protein is negligible as evidenced by CD spectroscopy. So, from these findings, we conclude that linezolid interacts with BSA in 1:1 ratio through hydrophobic, hydrogen bonding and ionic interactions, and this may not affect the secondary structure of the protein.