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Inhibitors of α‐amylase have been developed to regulate postprandial blood glucose fluctuation. The enzyme inhibition arises from direct or indirect inhibitor‐enzyme interactions, depending on inhibitor structures. However, an ignored factor, substrate, may also influence or even decide the enzyme inhibition. In this work, it is innovatively found that the difference in substrate enzymolysis modes, i.e., structural composition and concentration of α‐1,4‐glucosidic bonds, triggers the diversity in inhibitor‐enzyme aggregating behaviors and α‐amylase inhibition. For competitive inhibition, there exists an equilibrium between α‐amylase‐substrate catalytic affinity and inhibitor‐α‐amylase binding affinity; therefore, a higher enzymolysis affinity and concentration of α‐1,4‐glucosidic structures interferes the balance, unfavoring inhibitor‐enzyme aggregate formation and thus weakening α‐amylase inhibition. For uncompetitive inhibition, the presence of macromolecular starch is necessary instead of micromolecular GalG2CNP, which not only binds with active site but with an assistant flexible loop (involving Gly304‐Gly309) near the site. Hence, the refined enzyme structure due to the molecular flexibility more likely favors the inhibitor binding with the non‐active loop, forming an inhibitor‐enzyme‐starch ternary aggregate. Conclusively, this study provides a novel insight into the evaluation of α‐amylase inhibition regarding the participating role of substrate in inhibitor‐enzyme aggregating interactions, emphasizing the selection of appropriate substrates in the development and screening of α‐amylase inhibitors. [ABSTRACT FROM AUTHOR]

An important component of the pathogenicity of potentially pathogenic bacteria in humans is the urease enzyme. In order to avoid the detrimental impact of ureolytic bacterial infections, the inhibition of urease enzyme appears to be an appealing approach. Therefore, in the current study, morpholine-thiophene hybrid thiosemicarbazone derivatives (5a-i) were designed, synthesized and characterized through FTIR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. A range of substituents including electron-rich, electron- deficient and inductively electron-withdrawing groups on the thiophene ring was successfully tolerated. The synthesized derivatives were evaluated in vitro for their potential to inhibit urease enzyme using the indophenol method. The majority of compounds were noticeably more potent than the conventional inhibitor, thiourea. The lead inhibitor, 2-(1-(5-chlorothiophen-2-yl)ethylidene)- N-(2-morpholinoethyl)hydrazinecarbothioamide (5g) inhibited the urease in an uncompetitive manner with an IC50 value of 3.80 ± 1.9 μM. The findings of the docking studies demonstrated that compound 5g has a strong affinity for the urease active site. Significant docking scores and efficient binding free energies were displayed by the lead inhibitor. Finally, the ADME properties of lead inhibitor (5g) suggested the druglikeness behavior with zero violation. [ABSTRACT FROM AUTHOR]

The organophosphate insecticide chlorpyrifos (CPF), an acetylcholinesterase inhibitor, has raised serious concerns about human safety. Apart from inducing synaptic acetylcholine accumulation, CPF could also act at nicotinic acetylcholine receptors, like the α7-isoform (α7-nAChR), which could potentially be harmful to developing brains. Our aims were to use molecular docking to assess the binding interactions between CPF and α7-nAChR through, to test the neurocytotoxic and oxidative effects of very low concentrations of CPF on SH-SY5Y cells, and to hypothesize about the potential mediation of α7-nAChR. Docking analysis showed a significant binding affinity of CPH for the E fragment of the α7-nAChR (ΔGibbs: −5.63 to −6.85 Kcal/mol). According to the MTT- and Trypan Blue-based viability assays, commercial CPF showed concentration- and time-dependent neurotoxic effects at a concentration range (2.5–20 µM), ten-folds lower than those reported to have crucial effects for sheer CPF. A rise of the production of radical oxygen species (ROS) was seen at even lower concentrations (1–2.5 µM) of CPF after 24h. Notably, our docking analysis supports the antagonistic actions of CPF on α7-nAChR that were recently published. In conclusion, while α7-nAChR is responsible for neuronal survival and neurodevelopmental processes, its activity may also mediate the neurotoxicity of CPF. [ABSTRACT FROM AUTHOR]

Polyaromatic hydrocarbons (PAHs) pose a significant threat to ecosystems and human health due to their widespread presence and persistence in the environment. Conventional remediation techniques often fall short in both efficiency and environmental impact. However, recent advancements in utilizing organic macrocyclic host molecules show considerable promise for effectively sequestering and eliminating PAHs across diverse media. These macrocyclic host molecules play a central role in host–guest chemistry and supramolecular chemistry. It offers distinct advantages by virtue of their precisely tailored cavities and customizable functionalities, greatly enhancing their selective recognition abilities towards guest PAHs. The pursuit of designing and synthesizing novel functional macrocycles has captivated the attention of researchers, driven by the quest to address various challenges in supramolecular research. Over decades of dedicated exploration in host–guest chemistry and supramolecular chemistry, an expansive array of macrocyclic host molecules, constructed from diverse building blocks, have emerged as pivotal tools for encapsulating PAHs. This review presents an overview of the recent progress in the design, synthesis, and application of purely organic macrocyclic molecules in the encapsulation of PAHs. It elucidates the underlying principles that govern their ability to recognise PAHs, such as host–guest interactions, shape complementarity, and π-π stacking interactions. Furthermore, the review discusses various experimental methodologies, such as spectroscopic analyses, chromatography, and computational modelling, employed to assess the efficiency of organic cage molecules in PAH trapping. Additionally, considerations regarding the scalability and environmental implications of organic cage-based PAH trapping systems are addressed. The insights gleaned from this research provide valuable guidance for the development of robust strategies to combat PAH pollution in diverse environmental contexts.

Blue C-phycocyanin (C-PC), the major Spirulina protein with innumerable health-promoting benefits, is an attractive colourant and food supplement. A crucial obstacle to its more extensive use is its relatively low stability. This study aimed to screen various food-derived ligands for their ability to bind and stabilise C-PC, utilising spectroscopic techniques and molecular docking. Among twelve examined ligands, the protein fluorescence quenching revealed that only quercetin, coenzyme Q10 and resveratrol had a moderate affinity to C-PC (Ka of 2.2 to 3.7 × 105 M–1). Docking revealed these three ligands bind more strongly to the C-PC hexamer than the trimer, with the binding sites located at the interface of two (αβ)3 trimers. UV/VIS absorption spectroscopy demonstrated the changes in the C-PC absorption spectra in a complex with quercetin and resveratrol compared to the spectra of free protein and ligands. Selected ligands did not affect the secondary structure content, but they induced changes in the tertiary protein structure in the CD study. A fluorescence-based thermal stability assay demonstrated quercetin and coenzyme Q10 increased the C-PC melting point by nearly 5 °C. Our study identified food-derived ligands that interact with C-PC and improve its thermal stability, indicating their potential as stabilising agents for C-PC in the food industry. [ABSTRACT FROM AUTHOR]

There are many scientific reports on the interaction of the SARS‐CoV‐2 virus S protein (and its RBD) with the human ACE2 receptor protein. However, there are no reliable data on how this interaction differs from the interaction of the receptor binding domain of SARS‐CoV‐1 with ACE2, in terms of binding strength and changes in reaction enthalpy and entropy. Our studies have revealed these differences and the impact of zinc ions on this interaction. Intriguingly, the binding affinity of both RBDs (of SARS‐CoV‐1 and of SARS‐CoV‐2) to the ACE2 receptor protein is almost identical; however, there are some differences in the entropic and enthalpic contributions to these interactions.

Aiming to design unique metallic drugs with significant therapeutic activity, in this work, mixed ligand Cu (II) complex involving 2,2′‐bipyridine and phenylalanine [Cu (bpy) (phenala.)Cl].2H2O has been fabricated and characterized using IR spectroscopy. The interaction of Cu (II) complex with CT‐DNA molecules was examined through UV–vis absorption titration plots, thermal denaturation experiments, viscosity measurements, and electrochemical studies. Cyclic voltammetry, electrochemical impedance spectroscopy, and chronoamperometry measurements have been exploited to elucidate their binding style. The negative potential shift in ΔE and E1/2 values as well as the increased current density of Cu (II)/Cu(I) redox couple suggested the promoted rate of electron transfer process in presence of CT‐DNA molecules in the examined solution. Some kinetic parameters were also estimated such as the diffusion coefficient, the exchange current density, and Tafel slope values. Based on the results of these binding experiments, a groove and/or electrostatic interaction mode was expected. The antimicrobial activity of the studied Cu (II) complex was screened against a series of bacteria and fungi. An outstanding performance was shown when treating different Gram‐positive and Gram‐negative bacteria types. Moreover, an enhanced cytotoxicity behavior toward some human tumor cell lines, including MCF7, HEPG2, and HFB4, was detected with respective IC50 values of 43.02, 51.21, and >200 μM when incubated with Cu (II) complex for 72 h. These results suggest the application of [Cu (bpy) (phenala.)Cl].2H2O complex as a chemotherapeutic agent with a promising output in the drug discovery field. [ABSTRACT FROM AUTHOR]

With consumers gaining prominent awareness of health and well‐being, a diverse range of fortified or reformulated novel food is developed to achieve personalized or tailored nutrition using protein, carbohydrates, or fat as building blocks. Flavor property is a critical factor in the acceptability and marketability of fortified or reformulated food. Major food ingredients are able to interact with flavor compounds, leading to a significant change in flavor release from the food matrix and, ultimately, altering flavor perception. Although many efforts have been made to elucidate how food matrix components change flavor binding capacities, the influences on flavor perception and their implications for the innovation of fortified or reformulated novel food have not been systematically summarized up to now. Thus, this review provides detailed knowledge about the binding behaviors of flavors to major food ingredients, as well as their influences on flavor retention, release, and perception. Practical approaches for manipulating these interactions and the resulting flavor quality are also reviewed, from the scope of their intrinsic and extrinsic influencing factors with technologies available, which is helpful for future food innovation. Evaluation of food–ingredient interactions using real food matrices while considering multisensory flavor perception is also prospected, to well motivate food industries to investigate new strategies for tasteful and healthy food design in response to consumers' unwillingness to compromise on flavor for health. [ABSTRACT FROM AUTHOR]

Biological interactions often involve the transport of molecules, ions, or other species across biological membranes or between interacting proteins. The understanding of these transport phenomena is crucial for the development of therapies for various diseases. Atomic force microscopy is a powerful tool that has been increasingly used to study biological systems at the nano scale. The high resolution, quantitative measurements, and the ability to probe biological interactions under near-physiological conditions make AFM an attractive tool for investigating transport phenomena in biological systems. In this article, we focus on the use of AFM in the study of the transport phenomena in biological systems. We discuss the principles of AFM, its instrumentation, and its application in the study of biomolecules and biological systems. We also provide a comprehensive overview of recent articles that have utilized AFM in the study of biomarkers in biological systems. [ABSTRACT FROM AUTHOR]

Crustaceans are perishable with a short shelf-life. They are prone to deterioration after capture, particularly during handling, processing, and storage due to melanosis caused by polyphenoloxidase (PPO). Therefore, inhibitory effects of chitooligosaccharide (CHOS) in comparison with CHOS-catechin (CHOS-CAT), CHOS-epigallocatechin gallate (CHOS-EGCG), and CHOS-gallic acid (CHOS-GAL) conjugates on Pacific white shrimp cephalothorax PPO were studied. IC50 of CHOS-CAT (0.32 mg/mL) toward PPO was less than those of all conjugates tested (p < 0.05). CHOS-CAT exhibited the mixed-type inhibition. Kic (0.58 mg/mL) and Kiu (0.02 mg/mL) of CHOS-CAT were lower than those of other conjugates (p < 0.05). CHOS-CAT showed static fluorescence-quenching, suggesting a change in micro-environment around the active site of PPO. Moreover, CHOS-CAT was linked with various amino acid residues, including Tyr208 or Tyr209 of proPPO via van der Waals, hydrophobic interaction, and hydrogen bonding as elucidated by the molecular docking of proPPO. Although CHOS-CAT had the highest PPO inhibitory activity, it showed a lower binding energy (−8.5 kcal/mol) than other samples, except for CHOS-EGCG (−10.2 kcal/mol). Therefore, CHOS-CAT could act as an anti-melanosis agent in shrimp and other crustaceans to prevent undesirable discoloration associated with quality losses. [ABSTRACT FROM AUTHOR]

Tea polyphenol epigallocatechin-3-gallate (EGCG) has been previously explored as an effective inhibitor of carbohydrate hydrolyzing α-glucosidase for regulating postprandial blood glucose level. Proteins act as one common dietary component, the influence of which on α-glucosidase inhibition of EGCG remains unknown. In this study, bovine serum albumin (BSA) and isolated whey protein (IWP) were found to significantly weaken the competitive inhibitory activity of EGCG against α-glucosidase by the effect order of BSA > IWP, while egg albumin (EA) hardly influenced the enzyme inhibition. Through the analyses of kinetics, spectroscopy, thermodynamics and simulated docking, a protein-EGCG-enzyme ternary complex was suggested to generate in the interaction system, in which there existed competition between proteins (BSA and IWP) and α-glucosidase regarding formation of hydrogen bondings with polyphenolic groups (especially galloyl moiety). This weakened the EGCG-enzyme binding interactions at α-glucosidase active site, and thus reduced the enzyme inhibition in vitro and in vivo. However, there existed a co-existing relationship between proteins and α-glucosidase regarding π-stackings of EGCG benzene ring with aromatic residues of both macromolecules, which remained the fluorescence quenching ability of EGCG against the enzyme. Conclusively, dietary proteins should be considered as a potential influence factor when developing natural products as inhibitors of carbohydrate hydrolyzing enzymes. [Display omitted] • BSA and IWP decreased but EA remained α-glucosidase inhibition of EGCG. • A protein-EGCG-enzyme ternary complex generated with the polyphenol as a bridge. • Competition existed between proteins and enzyme for hydrogen bondings with EGCG. • Proteins remained π-stackings between EGCG benzene and enzyme aromatic residues. • Proteins weakened the regulation effect of EGCG on postprandial blood glucose. [ABSTRACT FROM AUTHOR]

There are many scientific reports on the interaction of the SARS‐CoV‐2 virus S protein (and its RBD) with the human ACE2 receptor protein. However, there are no reliable data on how this interaction differs from the interaction of the receptor binding domain of SARS‐CoV‐1 with ACE2, in terms of binding strength and changes in reaction enthalpy and entropy. Our studies have revealed these differences and the impact of zinc ions on this interaction. Intriguingly, the binding affinity of both RBDs (of SARS‐CoV‐1 and of SARS‐CoV‐2) to the ACE2 receptor protein is almost identical; however, there are some differences in the entropic and enthalpic contributions to these interactions. [ABSTRACT FROM AUTHOR]

Previous spectrophotometric investigations revealed strong binding affinities between four potential monoazo colourants (code-named AZ-01 to 04) and bovine serum albumin (BSA) which could dictate the tissue distribution and toxicity of the additives. The molecular docking interactions of the dyes with BSA were analyzed using AutoDock vina and PatchDock in order to elucidate the functional groups involved in complex stabilization. Docking conformations confirmed the ligands preferentially inserted into the hydrophobic cavities of BSA site I. Structure-BSA binding relationships revealed the binding of AZ-02 was driven by hydrogen bond donation from its free phydroxynaphthalene substituent to Ser-479 while the predominantly hydrazone form of its positional isomer, AZ-01, increased its lipophilicity and tendency for hydrophobic interactions. The relatively higher C/H ratio of AZ-03 and - 04, which contain additional C-7 substituents, was responsible for their stronger binding and the extensive involvement of their aromatic rings in ligand-site I complex stabilization via Pi-Pi T-shaped, Pi-alkyl and alkyl-alkyl interactions. Moreso, AZ-01, -03 and -04 exist predominantly as hydrazone tautomers with an overall positive charge which provided complementary modes for interaction with negatively charged aspartic and glutamic acids. The structure-BSA binding relationships of the molecules, which can be employed in synthesis of safer congeners, have been elucidated. [ABSTRACT FROM AUTHOR]

Catalase (CAT) is an essential protein protecting the cell from oxidative damage by reactive oxygen species. CAT is a heme enzyme in which iron metal plays a crucial role in catalytic activity. In this research, an iron (II, III) complex ([Fe (bpy)3] [Fe (dipic)2]2.7H2O; dipic−2 = pyridine‐2,6‐ dicarboxylato and bpy = 2,2′‐bipyridine) was used to evaluate its binding interactions with bovine liver catalase (BLC) using spectroscopic and molecular docking methods. The experimental results demonstrated that the catalytic activity of BLC increased slightly and reached 106% of the initial activity. The interactions between Fe complex and BLC led to the quenching of the catalase fluorescence emission via the static quenching mechanism. Thermodynamic parameters demonstrated that the predominant interactions between catalase and Fe complex are hydrogen bond and van der Waals and the process is exothermic and enthalpy driven. The circular dichroism (CD) and synchronous fluorescence results showed that the Fe complex altered the structure and conformation of BLC. It changed the secondary structure of BLC by decreasing α‐helix and β‐sheet content. Also, the experimental data were analyzed using Multivariate Curve Resolution–Alternating Least Square (MCR‐ALS) to the resolution of measured complex spectra and estimate the number of independent chemical species. The docking results in agreement with experimental data showed that the cationic part of the complex with catalase is mainly hydrophobic and van der Waals interactions, and for the anionic part are hydrophobic, van der Waals, and hydrogen bonding. [ABSTRACT FROM AUTHOR]

In this work, for the first time, we designed derivatives of beta-D-glucosyloxy-3-hydroxy-trans-stiblene-2-carboxylic acid (GHS), by conjugating GHS with tumor targeting peptides RPARPAR and GGKRPAR to target over-expressed receptors in tumor cells. The sequences RPARPAR and GGKRPAR are known to target the neuropilin1 (NRP1) receptor due to the C-terminal Arg domain; however, their effectiveness has never been examined with other commonly over-expressed receptors in tumor cells, particularly of chronic lymphocytic leukemia that include integrin α1β1 and CD22. By conjugating these peptides with GHS, which is known for its inherent anti-cancer properties, the goal is to further enhance tumor cell targeting by developing compounds that can target multiple receptors. The physicochemical properties of the conjugates and individual peptides were analyzed using Turbomole and COSMOthermX20 in order to determine their hydrogen bond accepting and donating capabilities. The web server POCASA was used in order to determine the surface cavities and binding pockets of the three receptors. To explore the binding affinities, we conducted molecular docking studies with the peptides and the conjugates with each of the receptors. After molecular docking, the complexes were analyzed using Protein–Ligand Interaction Profiler to determine the types of interactions involved. Molecular dynamics simulation studies were conducted to explore the stability of the receptor-ligand complexes. Our results indicated that in most cases the conjugates showed higher binding and stability with the receptors. Additionally, highly stable complexes of conjugates were obtained with CD22, NRP1 and in most cases with the integrin α1β1 receptor as well. The binding energies were calculated for each of the receptor ligand complexes through trajectory analysis using MMGBSA studies. SwissADME studies revealed that the compounds showed low GI absorption and were not found to be CYP inhibitors and had bioavailability score that would allow them to be considered as potential drug candidates. Overall, our results for the first time show that the designed conjugates can target multiple over-expressed receptors in tumor cells and may be potentially developed as future therapeutics for targeting tumor cells. [ABSTRACT FROM AUTHOR]

4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor is one of the important herbicides to solve the problem of weed control. With the widespread and continued use of HPPD inhibitor (HPPDi) herbicides, it may inevitably put pressure on the environment. Humic acid (HA) can effectively interact with pesticides through sorption or covalent bond formation and promote the degradation of pesticides, which can reduce the risk of pesticides in the environment. In the present study, the interactions of four HPPDi herbicides (sulcotrione, tembotrione, topramezone and mesotrione) with HA were reported and comparative assessment of the binding using multispectral technology, density functional theory (DFT) calculation and two-dimensional correlation spectroscopy (2D-COS). Time-resolved measurements and the Stern-Volmer constant at different temperature verified that HPPDi can bind with HA through the static quenching mechanism. From the thermodynamic parameters, the interaction force between HA and sulcotrione, tembotrione, topramezone and mesotrione was provided by electrostatic force. DFT, binding constant and three-dimensional (3D) fluorescence peak variation all indicated that the order of the binding ability of the four HPPDi and HA was mesotrione > tembotrione > sulcotrione > topramezone. According to dynamic light scattering (DLS), pH 7 is most conducive to the formation of HA-HPPDi complexes. Fourier transform infrared spectroscopy (FTIR) and 2D-COS showed that HA combined with HPPDi through aromatic C-H, CO and C-X, and the first binding group to HA was almost all CO. Sulcotrione, tembotrione, topramezone and mesotrione quench the endogenous fluorescence of HA by a static quenching mechanism and bind to HA through electrostatic interaction to form a complex. These results provide important insights into the combination of environmental pollutants with HA.

Objective: The free and active concentration of drugs and thereby their pharmacokinetic properties are controlled by their binding to human serum albumin (HSA) protein. Irbesartan (IRB), an antihypertensive drug was aimed to be investigated in terms of its binding interactions with different sites of HSA using in silico molecular docking technique along with the commonly employed spectroscopic techniques. Methods: Using FT-IR spectroscopy, the spectral shifting and intensity variations before and after complexation with IRB were studied for amide A, amide-I as well as amide-II of HSA. The absorbance of HSA with and without increasing concentrations of IRB was studied at 280 nm and the binding constant was determined using UV-spectroscopy. Molecular docking study was performed, and the types of interactions were predicted. Results: The IR spectra of IRB-HSA complex showed reductions in the intensities of amide-I and II bands as well as marked reduction in the α-helix content of HSA. The absorbance of HSA protein increased with increasing concentrations of drug. A binding constant value of 5.64 × 104 M−1 was calculated indicating good interaction. Molecular docking studies showed that IRB interacts more effectively with site-I of HSA through greater number of hydrogen bonds and strong π–charge (electrostatic) interactions than with site-II. Conclusions: The spectroscopic and molecular docking techniques proved to be effective tools to study the drug-protein interaction which provided accurate results as evident from these studies. Studying drug-albumin interaction is of utmost importance as it directly influences the overall pharmacokinetics of the drugs including its distribution, metabolism and therefore the duration of action.

The courses of starch digestion with individual α-amylase (AA), amyloglucosidase (AMG), and AA/AMG bi-enzyme system were performed and analyzed by first-order-reaction equations in the absence and presence of tannic acid (TA). An antagonistic effect between AA and AMG occurred at the digestion phase of readily-digestible starch due to the higher catalytic efficiency of AMG for starchy-substrates with more complex structures. This effect caused a faster rate of glucose production with AMG than with AA/AMG bi-enzyme system at this phase both in the absence and presence of TA. TA had a higher binding affinity to AA than to AMG as accessed by several methods, such as inhibition kinetics, fluorescence quenching, isothermal titration calorimetry (ITC), and molecular docking. Besides, differential scanning calorimetry (DSC) indicated that the change in the thermal and structural stabilities of enzymes in the presence of TA was related to the enzyme residues involved in binding with TA, rather than the inhibitory effects of TA. The binding characters of TA to both enzymes resulted in more “free” AMG without TA binding in AA/AMG bi-enzyme system than that in individual AMG. This binding property caused more and faster rate of glucose production at the digestion phase of slowly digestible starch (SDS) in the bi-enzyme system.

Ubiquitin‐like containing PHD and ring finger (UHRF)1 and UHRF2 are multidomain epigenetic proteins that play a critical role in bridging crosstalk between histone modifications and DNA methylation. Both proteins contain two histone reader domains, called tandem Tudor domain (TTD) and plant homeodomain (PHD), which read the modification status on histone H3 to regulate DNA methylation and gene expression. To shed light on the mechanism of histone binding by UHRF2, we have undergone a detailed molecular investigation with the TTD, PHD and TTD‐PHD domains and compared the binding activity to its UHRF1 counterpart. We found that unlike UHRF1 where the PHD is the primary binding contributor, the TTD of UHRF2 has modestly higher affinity toward the H3 tail, while the PHD has a weaker binding interaction. We also demonstrated that like UHRF1, the aromatic amino acids within the TTD are important for binding to H3K9me3 and a conserved aspartic acid within the PHD forms an ionic interaction with R2 of H3. However, while the aromatic amino acids in the TTD of UHRF1 contribute to selectivity, the analogous residues in UHRF2 contribute to both selectivity and affinity. We also discovered that the PHD of UHRF2 contains a distinct asparagine in the H3R2 binding pocket that lowers the binding affinity of the PHD by reducing a potential electrostatic interaction with the H3 tail. Furthermore, we demonstrate the PHD and TTD of UHRF2 cooperate to interact with the H3 tail and that dual domain engagement with the H3 tail relies on specific amino acids. Lastly, our data indicate that the unique stretch region in the TTD of UHRF2 can decrease the melting temperature of the TTD‐PHD and represents a disordered region. Thus, these subtle but important mechanistic differences are potential avenues for selectively targeting the histone binding interactions of UHRF1 and UHRF2 with small molecules. [ABSTRACT FROM AUTHOR]

Chronic wound resulting from diabetes mellitus is a significant cause of amputation worldwide. Secondary infections, lowering of nitric oxide synthase level, reduction of glucose-6-phosphate dehydrogenase levels, improper extracellular matrix remodelling, neuropathy, abnormality of endothelial cell function, and vasculopathy impedes the normal wound healing cycle during diabetes. Multiple studies have concluded that Ser9 phosphorylation causes inhibition of the glycogen synthase kinase-3β (GSK3-β) protein, which is essential for faster diabetic wound healing. Hence this protein could be a potential target for molecular interactions with prospective wound-healing molecules. Verbascoside, martynoside, echinacoside, crenatoside, and salidroside are a few phenylethanoid glycosides that have potential wound-healing ability by increasing extracellular matrix synthesis, angiogenesis, keratinocyte migration, and the functioning of macrophages and neutrophils. Thus, the five glycosides were subjected to molecular docking with GSK3-β protein (PDB ID: 1I09). This study revealed strong binding interactions with GSK3-β (between −10.2 and −7.3 kcal/mol) and inhibition constants (between 0.032 and 4.397 µM) which suggested potent inhibition of the target protein even at lower concentrations of these compounds. Further, the docked complexes were visualized to find the interaction of the ligands with the amino acid residues. However, further in vivo and in vitro studies are required to validate the activity of these phenylpropanoid glycosides in diabetic wound healing.

Aptamers are nucleic acids that can bind with high affinity and specificity to a range of target molecules. However, their functionality relies on their secondary and tertiary structures such that the combination of nucleotides determines their three-dimensional conformation. In this study, the binding mechanisms of candidate aptamers and their interactions with selected target proteins found in the cell surface of Leptospira were predicted to select high-affinity aptamers. Four aptamers were evaluated through molecular modeling and docking using available software and web-based tools, following the workflow previously designed for in silico evaluation of DNA aptamers. The most predominant and highly conserved surface-exposed proteins among pathogenic Leptospira species were used as aptamer targets. The highest number of interactions was seen in aptamers AP5 and AP1. Hydrogen bonds, along with a few hydrophobic interactions, occur in most aptamer–protein complexes. Further analysis revealed serine, threonine, glutamine, and lysine as main protein residues. H-bond interactions occur mostly with polar amino acids, as reflected in the predicted interaction profiles of aptamer–protein complexes. In silico strategies allowed the identification of key residues crucial in aptamer–target interaction during aptamer screening. Such information can be used in aptamer modification for improved binding affinity and accuracy for diagnostics application.

Phthalic acid esters (PAEs) are a group of widespread persistent organic pollutants in the environment. Though the harmful effect of PAEs including activity inhibition of superoxide dismutase (SOD) to arouse oxidative stress were well documented, the deep insights into mechanisms that are relevant with SOD activity are still lacking. By 7d-cultivation of Eisenia fetida in artificially-polluted soil, the different active responses of SOD in earthworm were shown to PAE congeners. Despite the less bioaccumulation and bioavailability, the di-butyl phthalate (DBP) etc. structurally coupled with longer ester-chains appeared more effective to trigger the up-regulation and then the slight decline of SOD activity. Given the remarkable biotransformation especially for short-chain PAEs, the SOD activity response in earthworm should be regarded as joint effect with their metabolites, e.g. monophthalates (MAEs) and phthalic acid (PA). The in vitro SOD activity was shown with the obvious inhibition of 21.31% by DBP, 88.93% by MBP, and 58.57% by PA respectively when the concentrations were elevated up to 0.03 mM. The SOD activity inhibition confirmed the molecular binding with pollutants as an essential event besides the biological regulation for activity. The binding interaction was thermodynamically exothermic, spontaneous and strengthened primarily by Van der Waals force and hydrogen bonds, and was spectrally diagnosed with the conformational changes including diminution of α-helix content and spatial reorientation of fluorophore tryptophan. As coherently illustrated with the larger fluorescence quenching constants (3.65*104–4.47*104/mol) than DBP, the metabolites should be the priority concern due to stronger activity inhibition and toxicological risks.

The inhibition mechanism of four caffeic and tartaric acid derivates, including caffeic acid (CA), tartaric acid (TA), caftaric acid (CFA) and chicoric acid (CHA) against α-glucosidase was characterized by substrate depletion, fluorescence quenching, isothermal titration calorimetry (ITC) and molecular docking. TA and CA were found with the highest and no inhibition effect respectively, and caffeoyl substitution at 2 and/or 3-OH of TA significantly decreased its inhibition. The enzyme inhibition effects of organic acids were not in an inhibitor concentration-dependent mode, and there was a rush increase in inhibition at a respective acidic pH value, especially for CFA and CHA, suggesting the important role of acidic pH in the enzyme inhibition for both compounds. Besides, CA, CFA and CHA were shown with strong quenching effects on α-glucosidase fluorescence because of π-conjugations between aromatic ring of caffeoyl moiety and that of enzyme fluorescent residues. However, no fluorescence quenching effect was observed for TA due to lack of aromatic ring. Additionally, a direct binding interaction behavior was observed for TA with α-glucosidase according to the fitted independent binding model in ITC, but not for CFA and CHA. Therefore, both acidic pH and binding interactions of TA with α-glucosidase resulted in the enzyme inhibition.

Acetylene is an important precursor in the petrochemical, plastics and electronic industries, as well as the prominent fuel for welding and metal cutting. The high flammability and explosive nature of acetylene, however hinder its safe storage and transportation. Porous materials are highly promising for acetylene storage and as they can provide strong binding interactions and an optimal pore environment. Furthermore, high selectivity and separation can be achieved for acetylene over other gases such as CO2 and small hydrocarbons. In this review, we divulge into the recent advancements and paradigms in acetylene storage and separation with a focus on porous metal‐organic frameworks (MOFs). An overview of the benchmark materials for acetylene storage and separation, along with some recent developments in the strategies to balance the trade‐off between the uptake capacity and selectivity is provided. The approaches of designing small pores and highly functionalized pore environments for strong binding with the acetylene adsorbate; along with the pore space partition, window space directed assembly and inverse CO2/C2H2 adsorption for the separation of acetylene from CO2, CH4, C2H4 and other hydrocarbons are reviewed to provide a summary and help further augment the research in this direction. [ABSTRACT FROM AUTHOR]

The casein hydrolysate peptides that had inhibitory activity against starch-hydrolyzing enzymes were explored and screened. After enzymolysis, dialysis, ultrafiltration, and lyophilization, hydrolysate peptides with molecular weight >3 k, 1-3 k and <1 k Da were obtained. The hydrolysates were determined with inhibitory activity against α-glucosidase, instead of α-amylase, and the active components concentrated in <1 k hydrolysates. By combination of HPLC-ESI-Q-TOF-MS/MS analysis, systematical evaluation, and simulated docking, 5 oligopeptides were screened from <1 k hydrolysates as the potential inhibitors of α-glucosidase, including SFFL, YPFP, PFA, LYGF and GPFPI. Then, 5 oligopeptide monomers were obtained through solid-phase synthesis and HPLC purification for inhibitory activity confirmation and mechanism elucidation. It was found that the inhibitory activity of the screened oligopeptides were significantly stronger than <1 k hydrolysates, with the intensity order of SFFL > LYGF ≈ YPFP ≈ GPFPI > FPA. The competitive inhibition character of SFFL and the uncompetitive inhibition characters of YPFP and FPA contributed to the mixed-type inhibition model of <1 k hydrolysates. SFFL could bind with the active site of α-glucosidase, forming the specific oligopeptide-enzyme binary complex. YPFP and FPA tended to bind with the enzyme-substrate, forming the oligopeptide-enzyme-substrate ternary complex, instead of directly binding with the enzyme. Considering the structure-activity relationship, the intensive hydrophobic amino acids, single hydrophilic amino acid, and four amino acid sequences favored the oligopeptides to interact with α-glucosidase through hydrophobic interactions, hydrogen bondings and ionic interactions. Due to the enzyme inhibition, the hydrolysate peptides could retard starch digestion both in vitro and in vivo , making it as a potential functional component for regulation of postprandial blood glucose level. [Display omitted] • Bovine casein hydrolysate peptides inhibited α-glucosidase, rather than α-amylase. • Active peptides concentrated in hydrolysate constituents with low molecular weight. • Five oligopeptides inhibiting α-glucosidase activity were screened and prepared. • There could form oligopeptide-enzyme and/or oligopeptide-enzyme-substrate complexes. • CaseIn hydrolysate peptides retarded starch digestion velocity in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Flavor profile is the most critical quality attribute of foods. Flavor binding ability is one of the most essential functional properties of the protein. The dynamic equilibrium of release and retention of volatile flavor compounds in protein-containing systems is known to largely influence the sensory quality and consumer acceptability of foods. Based on the protein-flavor systems, the protein source and conformational information plays a critical role in their interactions which are of great interest to flavor chemists. A fundamental review of the mechanism of protein-flavor interactions is discussed with a special emphasis on the protein aspect. The recent findings of mathematical models in describing the flavor retention and release in protein aqueous model have been summarized. The flavor binding abilities of animal protein and plant protein are systematically compared. The recent advances of the extrinsic factors including the processing methods affecting the interaction of protein-flavor binding are highlighted. Finally, future considerations and the trend of future research are presented and investigated. The knowledge about the mathematical models describing protein-flavor interactions is essential for the qualitatively and quantitatively prediction for flavor binding behaviors. The interaction between flavor compounds and proteins from plant needs more investigations. The extrinsic or environmental factors in food systems can affect the protein-flavor interactions but some contradictory conclusions should be further evaluated. Future studies will further focus on the sensory evaluation and the relationship between sensory quality and strength of protein-flavor binding. • Mathematical models are essential for predicting flavor binding behaviors. • The interaction between flavor and protein from plant needs more investigations. • The extrinsic or environmental factors affect the protein-flavor interactions. • The sensory quality and protein-flavor binding in foods need further studies. [ABSTRACT FROM AUTHOR]

Herein, the solution properties of Triton X-100 (TX-100) and polyethylene glycol (PEG) mixtures in H2O and salt (potassium, sodium, and ammonium) solutions have been observed through the cloud point (CP) detection technique. The present observation reveals that the values of CP of the TX-100 + PEG mixed solution, in the presence of different salts, undergo a decrease compared to the values found in H2O medium. The anion of common salts, such as sodium, potassium, and ammonium, was found to reduce the values of CP in the sample mixtures in the order: SO42− > Cl− > PO43−. The Δ G c 0 value was calculated as positive in all experimental cases, and this observation manifests a non-spontaneous nature of clouding system. The non-spontaneity of TX-100 + PEG clouding process was gradually declined with the enhancement of salt concentrations. The Δ H c 0 and Δ S c 0 values were found negative, which experience a decrease with the addition of more concentrated salt solutions in almost all of the cases studied. The negative values of Δ H c 0 and Δ S c 0 indicate the existence of exothermic interactions (hydrogen bonding and weak dipole–dipole forces) operating between TX-100 and PEG. A linear relationship was established between Δ H c 0 and Δ S c 0 with R2 values in the range of 0.9997–1.00. [ABSTRACT FROM AUTHOR]

Densities, ρ, and Speeds of Sound, u, were measured for pure liquids of ethyl acetate, (EtOAc), 1,2-butanediol, (1,2-BD), 1,3-butanediol, (1,3-BD), 1,4-butanediol, (1,4-BD) and their binary mixtures {x1 EtOAc + x21,2-BD}, { x1 EtOAc + x21,3-BD}, and { x1 EtOAc + x21,4-BD} over the composition (EtOAc) and at temperatures (298.15–323.15) K at pressure 0.1 MPa. To understand the molecular interactions of solute–solvent, measured excess properties such as the excess molar volume, V m E , excess isentropic compressibility, κ s E , excess speeds of sound, u E , excess molar isentropic compressibility, K s , m E , thermal expansion coefficient, α p , excess thermal expansion coefficient, α p E were calculated and fitted using the Redlich–Kister equation. For better understanding, also calculated partial molar volumes/isentropic compressibilities, and their excess properties at infinite dilution were measured. These parameters have been used to understand the interactions in the mixtures qualitatively. The experimental V m E findings were compared through the usage of theoretical model developed by Prigogine–Flory–Patterson (PFP). [ABSTRACT FROM AUTHOR]

α-Amylase is a key enzyme of starch digestion, playing an important role in deciding glucose releasing amount. Inhibition of the enzyme activity by polyphenols is suggested as a potential approach in controlling starch digestion and regulating postprandial hyperglycaemia. α-Amylase inhibition by polyphenols results from polyphenol-enzyme binding interactions that have been characterized by inhibition kinetics, spectroscopy and thermodynamic analyses. To further elucidate the inhibition mechanism, making the inhibition visible, studies regarding biochemical, biophysical and molecular mechanisms are summarized. Macroscopically, α-amylase inhibition causes retarded digestion of starchy substrates, visible from the production reaction color or fluorescence. Microscopically, detail inhibition kinetics reveals the inhibition types and theoretic interacting sites. X-ray diffraction (XRD) is powerful in extracting the binding modes (detail amino acid residues, polyphenol moieties and interaction forces involved in polyphenol-amylase interactions). Through polyphenol-amylase binding analysis by XRD and NOE correlation of polyphenol atoms by rotating-frame Overhauser enhancement spectroscopy (ROESY)-NMR, the contribution of intramolecular interactions between polyphenol ring-groups to the binding is evaluated. The key phenolic moieties for binding are also obtained by saturation transfer difference (STD)-NMR and/or molecular docking. Besides, by combing fluorescent properties and thermal stability of α-amylase, the enzyme conformational changes may be obtained. Additionally, following delayed starch digestion, α-amylase inhibition is indicated by retarded increase in blood glucose level and colonic fermentation properties of undigested starch. Conclusively, visible characterization helps to understand how a polyphenol develops the inhibitory activity, and to reasonably explore functional factors for alleviation of carbohydrate metabolism disorder. • Detail inhibition kinetics reveals the inhibition types, constants and binding sites. • XRD describes amino acid residues, polyphenol moieties, forces involved in inhibition. • STD-NMR and molecular docking indicate phenolic moieties in polyphenol-enzyme binding. • FQ and DSC characterize conformational changes of α-amylase by polyphenol binding. • Amylase inhibition may be indicated by blood glucose level and microbial fermentation. [ABSTRACT FROM AUTHOR]

Enzyme catalysis is an emerging technique that has been employed to identify the protein of interest in a complex cellular environment. In present article, we have utilized optical techniques for the identification of enzyme mediated catalysis of fusion protein to study the short chain amino acid epitope in both aqueous solution and cellular environment. We characterized enzyme catalysis short chain peptide with electron microscopic techniques, for the study of reaction product and its morphology in aqueous solution. Furthermore, we applied MALDI-TOF-MS technique for the analysis of fusion protein, FLAG-tag peptides and enterokinase enzyme (EK), in complex solutions and cellular environment. The enzyme catalytic reactions were studied HEK-293T cells with confocal fluorescence microscopy. In spectroscopic studies two sharp prominent peaks at 310 nm and 330 nm were appeared in case of Flag-tag peptide and for fusion protein absorption peaks were found at 315 nm and 410 nm with relative increase in intensity level. Furthermore, a linear relation between response unit and binding time (ms) for both fusion protein and EK was observed. Mass spectra reveal the presence of FLAG-tag peptide epitope at mass to charge (m/z) ratio of 2190.023 and 2191.102 in cell lysation with and without enterokinase respectively. We provide here a rapid and accurate trace detection system for enzyme cleaved peptides in fusion protein by taking a snapshot of peptide to identify specific domains based on amino acids and their mass spectrum calculations. [ABSTRACT FROM AUTHOR]

[Display omitted] Activin receptor‑like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-β (TGF-β) family. (TGF-β) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK5 inhibitors. In this review, we shed light on the current ATP-competitive inhibitors of ALK5 through diverse heterocyclic based scaffolds that are in clinical or pre-clinical phases of development. Moreover, we focused on the binding interactions of the compounds to the ATP binding site and the structure–activity relationship (SAR) of each scaffold, revealing new scopes for designing novel candidates with enhanced selectivity and metabolic profiles. [ABSTRACT FROM AUTHOR]

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.

Lawsone itself exhibits interesting biological activities, and its complexation with a metal center can improve the potency. In this context a cytotoxic Ru-complex, [Ru(law)(dppb)(bipy)] (law = lawsone, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2′-bipyridine), named as CBLAU, was prepared as reported. In this work, NMR binding-target studies were performed to bring to light the most accessible interaction sites of this Ru-complex toward Calf-Thymus DNA (CT-DNA, used as a model), in a similar approach used for other metallic complexes with anti-cancer activity, such as cisplatin and carboplatin. Advanced and robust NMR binding-target studies, among them Saturation Transfer Difference (STD)-NMR and longitudinal relaxometry (T1), were explored. The 1H and 31P -NMR data indicate that the structure of Ru-complex remains preserved in the presence of CT-DNA, and some linewidth broadening is also observed for all the signals, pointing out some interaction. Looking at the binding efficiency, the T1 values are highly influenced by the formation of the CBLAU-DNA adduct, decreasing from 11.4 s (without DNA) to 1.4 s (with DNA), where the difference is bigger for the lawsone protons. Besides, the STD-NMR titration experiments revealed a stronger interaction (KD = 5.9 mM) for CBLAU-DNA in comparison to non-complexed lawsone-DNA (KD = 34.0 mM). The epitope map, obtained by STD-NMR, shows that aromatic protons from the complexed lawsone exhibits higher saturation transfer, in comparison to other Ru-ligands (DPPB and bipy), suggesting the supramolecular contact with CT-DNA takes place by the lawsone face of the Ru-complex, possibly by a spatial π-π stacking involving π-bonds on nucleic acids segments of the DNA chain and the naphthoquinone group.

Polyphenols, as one group of secondary metabolite, are widely distributed in plants and have been reported to show various bioactivities in recent year. Starch digestion not only is related with food industrial applications such as brewing but also plays an important role in postprandial blood glucose level, and therefore insulin resistance. Many studies have shown that dietary phenolic extracts and pure polyphenols can retard starch digestion in vitro, and the retarding effect depends on the phenolic composition and molecular structure. Besides, dietary polyphenols have also been reported to alleviate elevation of blood glucose level after meal, indicating the inhibition of starch digestion in vivo. This review aims to analyze how dietary polyphenols affect starch digestion both in vitro and in vivo. We can conclude that the retarded starch digestion in vitro by polyphenols results from inhibition of key digestive enzymes, including α-amylase and α-glucosidase, as well as from interactions between polyphenols and starch. The alleviation of postprandial hyperglycemia by polyphenols might be caused by both the inhibited starch digestion in vivo and the influenced glucose transport. Therefore, phenolic extracts or pure polyphenols may be alternatives for preventing and treating type II diabetes disease. [ABSTRACT FROM AUTHOR]

• ρ and u have been measured of ethyl butyrate with isomeric butanediols between 298.15 and 323.15 K. • Thermophysical parameters have been calculated. • The effect of temperature has been discussed on excess derived properties in terms of intermolecular interactions. • The influence of intra molecular hydrogen bond was analyzed and it is high for 1,4-butanediol. Today biofuels are emerging in an exponentially manner in order to replace the fossil fuels. Biofuels are composed of several organic compounds containing wide variety of functional groups. The interactions existing among these compounds play a significant role in the efficiency of the biofuels. In this paper, the authors presented the new findings related to interactions existing in ethylbutyrate and α, ω -alkanediols in pure state as well as in their mixtures. Densities and speeds of sound at various temperatures (298.15–323.15) K and at ambient pressure 0.1 MPa have been measured for these mixtures. From experimental data, the excess properties such as excess molar volume, V m E , excess isentropic compressibility, κ s E , excess molar isentropic compressibility, K s , m E , excess speed of sound, u E , and excess isobaric thermal expansion, α p E , of the investigated mixtures were calculated. All the excess parameter values were fitted using the Redlich-Kister polynomial smoothing equation. The results were analysed in terms of molecular interactions. The partial molar volumes, V ¯ m,1 and V ¯ m,2 , partial molar isentropic compressibilities, K ¯ s,m,1 and K ¯ s,m,2 , excess partial molar volumes, V ¯ m,1 E and V ¯ m,2 E and excess partial molar isentropic compressibilities, K ¯ s,m,1 E and K ¯ s,m,2 E over whole composition range; the excess partial molar quantities of the components at infinite dilution have been calculated. The variations of these parameters with change in composition and temperature have been discussed in terms of intermolecular interactions prevailing in these mixtures. The V m E values for these mixtures were also calculated by using Prigogine–Flory–Patterson (PFP) theory and the results were compared with experimental findings. [ABSTRACT FROM AUTHOR]

Highlights • Binding of young apple polyphenols with α-amylase is an exothermal process. • Interaction constant values are in the similar orders for pure polyphenols. • α-Amylase inhibition by young apple polyphenols results from binding with the enzyme. • Young apple polyphenols can partially unfold the α-amylase structure. • The in-vitro and in-silico methods can be combined to reveal the interaction mechanism. Abstract The binding interactions between young apple polyphenols and porcine pancreatic α-amylase were investigated through isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) and molecular docking. The results obtained were compared with those obtained through inhibition kinetics and fluorescence quenching. It was found that binding of tannic acid, chlorogenic acid, caffeic acid and epicatechin with α-amylase is an exothermal process, with the binding constants in the order of tannic acid > chlorogenic acid > caffeic acid > epicatechin. This is consistent with the orders of reciprocal of competitive inhibition constant and fluorescence quenching constant. The binding energy obtained through molecular docking showed the same order, except for epicatechin. These results are consistent with the inhibition of α-amylase being caused by the binding of the polyphenols with the enzyme. In addition, from the fluorescence quenching and DSC data, total polyphenols, tannic acid, chlorogenic acid and caffeic acid were found to partially unfold the enzyme structure. [ABSTRACT FROM AUTHOR]

The effects of mixing orders of tannic acid (TA), starch, and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with the opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Moreover, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol has an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

• TCS induced the changes in the secondary structure of HSA. • TCS was tightly embedded in the site I of HSA. • Inhibition of esterase activity by TCS was an anti-competitive inhibition. • Trp214 and Lys199 were involved in the formation of the HSA-TCS complex. Triclosan (TCS) is an extensively distributed environmental contaminant that can have impacts on ecosystems and human health. This study employed both in vitro experiments and computer simulations to assess the interaction between TCS and human serum albumin (HSA) at the molecular level. The formation of the HSA-TCS complex was a spontaneous process, maintained by strong affinity (Ka > 105) due to hydrogen bonds and van der Waals forces. TCS binding to the I site of HSA led to an increase in hydrophobicity around the Trp-residue and altered the structure of the peptide chain backbone. CD spectroscopy revealed alterations in the secondary structure of HSA, including decreased α-helical content and increased disorder, in the presence of TCS. Moreover, the esterase activity in HSA was inhibited by TCS as an anticompetitive inhibitor. Molecular docking studies identified TCS tightly embedded at site I of HSA, with binding facilitated through hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations highlighted the significant energy contributions of Trp214 and Lys199 residues, directly involved in the formation of the HSA-TCS complex. Additionally, the presence of TCS enhanced the compactness of the HSA structure. Therefore, new insights into toxicological studies of other contaminants can be proposed based on these results of TCS. [Display omitted] [ABSTRACT FROM AUTHOR]

Molecular modeling is the technique to determine the overall structure of an unknown molecule, be it a small one or a macromolecule. The technique encompasses the method of screening ligand libraries for the development of new candidate drug molecules. All these aspects have become an essential topic of research. This field is truly interdisciplinary and finds its applications in almost all fields of life science research. In this chapter, an overview of the protocol associated with molecular modeling techniques will be discussed., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Coronavirus, an extremely contagious infections disease had a harmful effect on the world's population. It is a family of enveloped, single-stranded, positive-strand RNA viruses of Nidovirales order belongs to coroviridae family. At present, worldwide several lakhs of deaths and several billions of infections have been reported. Hence, the focus of the present study was to assess the SARS-CoV-2 enzyme inhibitory potential of certain commercially available terpenoids using Lamarckian genetic algorithm as a working principle and molecular dynamic studies was also performed. AutoDock 4.2 software was used to perform the computational docking calculations of terpenoids against SARS-CoV-2 enzyme. The terpenoids such as, Andrographolide, Betulonic acid, Erythrodiol, Friedelin, Mimuscopic acid, Moronic acid, and Retinol were selected based on the drug likeness properties. Remdesivir a well-known anti-viral drug was selected as the standard drug. Molecular dynamic simulation studies were carried using Desmond module of Schrodinger Suite. In the current study we observed that, Friedelin was exhibited excellent SARS-CoV-2 enzyme inhibitory potential than the standard drug and other selected terpenoids. Friedelin and the standard Remdesivir was undergone the molecular dynamic studies and Friedelin showed a good number of hydrogen bonds over the simulation time of 100 ns. Based on the in silico computational evaluation, it can be concluded that Friedelin could be worthwhile terpenoid against SARS-CoV-2 spike protein. A further study on Friedelin is required to develop a potential chemical entity against the management of COVID disease.Communicated by Ramaswamy H. Sarma.

The study of biomolecular interactions is crucial to get more insight into the biological system. The interactions of protein-protein, protein-nucleic acids, protein-sugars, nucleic acid-nucleic acids and protein-small molecules are supporting therapeutics and technological developments. Recently, the development in a large number of analytical techniques for characterizing biomolecular interactions reflect the promising research investments in this field. In this review, microscale thermophoresis technology (MST) is presented as an analytical technique for characterizing biomolecular interactions. Recent years have seen much progress and several applications established. MST is a powerful technique in quantitation of binding events based on the movement of molecules in microscopic temperature gradient. Simplicity, free solutions analysis, low sample volume, short analysis time, and immobilization free are the MST advantages over other competitive techniques. A wide range of studies in biomolecular interactions have been successfully carried out using MST, which tend to the versatility of the technique to use in screening binding events in order to save time, cost and obtained high data quality. [ABSTRACT FROM AUTHOR]

The influence of three proteins on α-amylase inhibition of by tannic acid (TA, a typical phenolic competitive inhibitor) were studied. It was found that bovine serum albumin (BSA) and isolated whey protein (IWP) significantly decreased the inhibitory activity of TA against α-amylase with the decreasing effect in the order of BSA > IWP, while egg albumin (EA) hardly affected the enzyme inhibition. TA interacted with both α-amylase and the proteins through non-covalent forces, including hydrogen bondings and π-stackings. The binding affinity of TA to three proteins followed the order of BSA > IWP > EA. Therefore, the similar order in the influence of three proteins on TA-amylase binding interactions was observed, resulting in the respective strongest and weakest decreasing effects of BSA and EA on α-amylase inhibition by TA. Interestingly, the proteins maintained the quenching effect of TA on α-amylase fluorescence. These results indicated that there formed a respective protein-TA-amylase ternary complex, in which TA-protein binding interactions maintained π-stacking between TA and α-amylase but weakened hydrogen bondings between TA and the enzyme active site. Therefore, the competitive inhibition intensity of TA was reduced by BSA and IWP. Conclusively, proteins should be considered as an influencing factor of dietary polyphenols regarding the regulation of starch digestion. [Display omitted] • BSA and IWP decrease, but EA maintains inhibitory activity of TA against α-amylase. • TA-protein binding affinity conform influence ability of protein on enzyme inhibition. • BSA and IWP decrease competitive inhibition, but remain fluorescence quenching of TA. • Protein-TA-amylase tricomplex forms due to TA-protein and TA-enzyme binding behaviors. • Tricomplex reduces hydrogen bondings but remains π-stackings in TA-enzyme interaction. [ABSTRACT FROM AUTHOR]

Ruthenium(II) arene PTA (1,3,5-triaza-7-phosphaadamantane) type complexes with curcuminoid ligands have attracted great attentions in biomedical areas. Investigation of structural influences helps in understanding the biological effects of these complexes. To research their structural influences, the interactions between two ruthenium(II) arene PTA type complexes with curcuminoid ligands and human serum albumin (HSA) were systematically investigated by multispectroscopic techniques and electrochemical methods. The fluorescence spectral results indicated that two complexes bonded with Sudlow's site I of HSA to form 1: 1 complex−HSA compounds. Van der Waals interactions and hydrogen bonds formation were the major binding forces during their complex formation interactions. Subsequently, the intrinsic fluorescence of HSA was statically quenched by these complexes through concentration-dependent manner. The conformation and secondary structure of HSA were all changed at the present of two complexes. The space steric hindrance of complexes was responsible for differences in the fluorescence quenching, while the chemical polarity played important role in the variation of binding interactions between HSA and two complexes. These results provide the molecular understanding of binding interactions between protein and ruthenium(II) arene PTA type complexes with curcuminoid ligands, which gain new insight into the biological applications of similar ruthenium(II) arene derivatives in the future. [ABSTRACT FROM AUTHOR]

Pyridine and its derivatives are widely used in many applications and inevitably cause extreme scenarios of serious soil contamination, which pose a threat to soil organisms. Still, the eco-toxicological effects and underlying mechanisms of pyridine-caused toxicity toward soil fauna have not been well established. Thus, earthworms (Eisenia fetida), coelomocytes, and oxidative stress-related proteins were selected as targeted receptors to probe the ecotoxicity mechanism of extreme pyridine soil exposure targeted to earthworms by using a combination of in vivo animal experiments, cell-based in vitro tests, in vitro functional and conformational analyses, and in silico analyses. The results showed that pyridine caused severe toxicity to E. fetida at extreme environmental concentrations. Exposure of pyridine induced excessive ROS formation in earthworms, causing oxidative stress and various deleterious effects, including lipid damage, DNA injury, histopathological change, and decreased defense capacity. Also, pyridine destroyed the cell membrane of earthworm coelomic cells and triggered a significant cytotoxicity. Importantly, the intracellular ROS (e.g., O 2 −, H 2 O 2 , and OH·–) was release-activated, which eventually inducing oxidative stress effects (lipid peroxidation, inhibited defense capacity, and genotoxicity) through the ROS-mediated mitochondrial pathway. Moreover, the antioxidant defence mechanisms in coelomocytes responded quickly to reduce ROS-mediated oxidative injury. It was conformed that the abnormal expression of targeted genes associated with oxidative stress in coelomic cells was activated after pyridine exposure. Particularly, we found that the normal conformation (particle sizes, intrinsic fluorescence, and polypeptide backbone structure) of CAT/SOD was destroyed by the direct binding of pyridine. Furthermore, pyridine bound easily to the active center of CAT, but preferentially to the junction cavity of two subunits of SOD, which is considered to be a reason for impaired protein function in cells and in vitro. Based on these evidences, the ecotoxicity mechanisms of pyridine toward soil fauna are elucidated based on multi-level evaluation. [Display omitted] • The ecotoxicity mechanisms of extreme pyridine soil exposure were explored. • Pyridine caused severe toxicity to E. fetida at extreme environmental concentrations. • Pyridine triggered oxidative stress through the ROS-mediated mitochondrial pathway. • Pyridine exposure induced the abnormal expression of oxidative stress-related genes. • The normal conformation and function of CAT/SOD was destroyed by pyridine binding. [ABSTRACT FROM AUTHOR]