Conformational Changes Of Human Serum Albumin Research Articles

Deciphering the binding mechanisms of eugenol and 2-methylpyrazine with human serum albumin using technical approach

Eugenol (EGL) and 2-methylpyrazine (2-MTP) are common food additives that are used as flavors in a variety of foods. To study the effect of food additives on human serum albumin (HSA), it is necessary to deeply study the interaction of EGL and 2-MTP with HSA. Fluorescence, UV–vis absorption, circular dichroism (CD) and computational techniques showed EGL and 2-MTP bind statically to HSA, inducing conformational changes of HSA. We calculated the quenching constants (ksv), binding constants (kq), binding distances (r) and thermodynamic constants (ΔH0, ΔS0, ΔG0) at four different temperatures. Based on thermodynamic analysis and molecular dynamics (MD) simulations, the main forces of 2-MTP-HSA and EGL-HSA systems are hydrophobic interaction and π-π accumulation, respectively. In addition, the interaction alters the physiological activity of HSA, esterase activity and free radical scavenging ability. This study provides valuable insights into the molecular interactions of food additive compounds EGL and 2-MTP with HSA, the findings provide theoretical reference for the development of new food additives and drugs in the future.

Spectroscopic investigation and structural simulation in human serum albumin with hydroxychloroquine/Silybum marianum and a possible potential COVID-19 drug candidate.

In this study, the interaction between human serum albumin (HSA) and the hydroxychloroquine/Silybum marianum (HCQ/SM) mixture was investigated using various techniques. The observed high binding constant (Kb) and Stern-Volmer quenching constant (KSV) indicate a strong binding affinity between the HCQ/SM mixture and HSA. The circular dichroism (CD) analysis revealed that HCQ/SM induced conformational changes in the secondary structure of HSA, leading to a decrease in the α-helical content. UV-Vis analysis exhibited a slight redshift, indicating that the HCQ/SM mixture could adapt to the flexible structure of HSA. The experimental results demonstrated the significant conformational changes in HSA upon binding with HCQ/SM. Theoretical studies were carried out using molecular dynamics simulation via the Gromacs simulation package to explore insights into the drug interaction with HSA-binding sites. Furthermore, molecular docking studies demonstrated that HCQ/SM-HSA exhibited favorable docking scores with the receptor (5FUZ), suggesting a potential therapeutic relevance in combating COVID-19 with a value of -6.24 kcal mol-1. HCQ/SM exhibited stronger interaction with both SARS-CoV-2 virus main proteases compared to favipiravir. Ultimately, the experimental data and molecular docking analysis presented in this research offer valuable insights into the pharmaceutical and biological properties of HCQ/SM mixtures when interacting with serum albumin.

Effects of ultraviolet radiation and reactive oxygen species on the structure and ligand-binding ability of human serum albumin for norfloxacin

To explore the influence of ultraviolet radiation (UV) and reactive oxygen species (ROS) on the structure and ligand-binding ability of human serum albumin (HSA) for norfloxacin (NFLX), HSA was treated with UV (HSAUV) and UV/H2O2 (HSAUV/H2O2), respectively. The structure difference of HSA, HSAUV and HSAUV/H2O2 were investigated by Fourier transform infrared, fluorescence (i.e., emission fluorescence, synchronous fluorescence and fluorescence lifetime) and circular dichroism spectroscopy. The intermolecular interactions of HSA, HSAUV and HSAUV/H2O2 with NFLX were studied at pH 7.4 and temperatures 291, 310, and 318 K, using fluorescence emission and synchronous fluorescence spectroscopy, and combined with molecular docking. The results suggested that UV and ROS could destroy the α-helix of HSA and induce the loose of HSA structure, and the average fluorescence lifetimes of HSA decreased from 6.12 ns to 3.76 ns (HSAUV) and 3.40 ns (HSAUV/H2O2). The conformational changes of HSA caused by UV and ROS allowed NFLX to get access to more potential binding sites and promoted the binding affinity of HSA for NFLX, while the temperature stability of the HSA-NFLX complex significantly decreased. The results are useful and valuable for evaluating the protein damage caused by UV and ROS in organisms.

Insights into interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin via multi-spectral analysis

In this study, the interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin (HSA) are investigated through UV–vis, fluorescence, and circular dichroism (CD) spectra. The mechanisms on the fluorescence quenching of HSA initiated by triazine herbicides are obtained using Stern-Volmer, Lineweaver-Burk and Double logarithm equations. The quenching rate constant (Kq), Stern-Volmer quenching constant (Ksv), binding constant (KA), thermodynamic parameters such as enthalpy change (∆H), entropy change (∆S) and Gibbs free energy (∆G) and number of binding site (n) are calculated and compared. The variations in the microenvironment of amino acid residues are studied by synchronous fluorescence spectroscopy. The binding sites and subdomains are identified using warfarin and ibuprofen as site probes. The conformational changes of HSA are measured using CD spectra. The results reveal that the triazine herbicides with different alkyl groups can interact with HSA by static quenching. The combination of the three herbicides and HSA are equally proportional, and the binding processes are spontaneous. Hydrophobic interaction forces play important roles in simetryne-HSA and ametryn-HSA, while the interaction of terbutryn-HSA is Van der Waals forces and hydrogen bonding. Moreover, the three herbicides can bind to HSA at site I (sub-domain IIA) more than site II (subdomain IIIA), and combine with tryptophan (Trp) more easily than tyrosine (Tyr) residues, respectively. By comparison, the order of interaction strength is terbutryn-HSA > ametryn-HSA > simetryne-HSA. Terbutryn can destroy the secondary structure of HSA more than simetryne and ametryn, and the potential toxicity of terbutryn is higher. It is expected that the interactions of triazine herbicides with HSA via multi-spectral analysis can offer some valuable information for studying the toxicity and the harm of triazine herbicides on human health at molecular level in life science.

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications.

Tetramethrin (TMT) is a commonly used insecticide and has a carcinogenic and neurodegenerative effect on humans. The binding mechanism and toxicological implications of TMT to human serum albumin (HSA) were examined in this study employing a combination of biophysical and computational methods indicating moderate binding affinity and potential hepato and renal toxicity. Fluorescence quenching experiments showed that TMT binds to HSA with a moderate affinity, and the binding process was spontaneous and predominantly enthalpy-driven. Circular dichroism spectroscopy revealed that TMT binding did not induce any significant conformational changes in HSA, resulting in no changes in its alpha-helix content. The binding site and modalities of TMT interactions with HSA as computed by molecular docking and molecular dynamics simulations revealed that it binds to Sudlow site II of HSA via hydrophobic interactions through its dimethylcyclopropane carboxylate methyl propanyl group. The structural dynamics of TMT induce proper fit into the binding site creating increased and stabilizing interactions. Additionally, molecular mechanics-Poisson Boltzmann surface area calculations also indicated that non-polar and van der Waals were found to be the major contributors to the high binding free energy of the complex. Quantum mechanics (QM) revealed the conformational energies of the binding confirmation and the degree of deviation from the global minimum energy conformation of TMT. The results of this study provide a comprehensive understanding of the binding mechanism of TMT with HSA, which is important for evaluating the toxicity of this insecticide in humans.

Investigation of the interaction between S-isoalkyl derivatives of the thiosalicylic acid and human serum albumin

S-isoalkyl derivatives of thiosalicylic acid (isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) were selected in order to investigate the binding interaction with the human serum albumin (HSA) using different spectroscopic methods and molecular docking simulation. Association constants and number of binding sites were used to analyze the quenching mechanism. The experimental results showed that the fluorescence quenching of HSA by L1, L2 and L3 occurs because of static quenching and that binding processes were spontaneous, with the leading forces in bonding by hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Fluorescence spectroscopy, UV-Vis spectroscopy and synchronous fluorescence spectroscopy showed that ligands (L1, L2 and L3) can bind to HSA and that the binding of ligands induced some microenvironmental and conformational changes in HSA. The calculated distance between the donor and the acceptor according to fiFörster’s theory confirms the energy transfer efficiency between the acceptor and HSA. Results of site marker competitive experiments showed that the tested compounds bind to HSA in domain IIA (Site I). Molecular dynamics and docking calculations demonstrated that L3 binds to the Sudlow site I of HSA with lower values of binding energies compared to L1 and L2, indicating the formation of the most stable ligand-HSA complex. Understanding the binding mechanisms of S-isoalkyl derivatives of the thiosalicylic acid to HSA may provide valuable data for the future studies of their biological activity and application as potential antitumor drugs. Communicated by Ramaswamy H. Sarma

Interactions between gold nanoparticles with different morphologies and human serum albumin

Introduction: Three different shapes of gold nanoparticles were synthesized in this experiment. At the same time, studies compared their effects with human serum albumin (HSA).Methods: Gold nanoparticles (AuNPs) with three different morphologies, such as, nanospheres (AuNSs), nanorods (AuNRs), and nanoflowers (AuNFs) were synthesized via a seeding method and their characteristic absorption peaks were detected using ultraviolet-visible (UV-vis) absorption spectroscopy, Telectron microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta potential measurements, circular dichroism (CD), and Fourier transform infrared spectroscopy (FTIR) to study the interactions between them and HSA. By comparing the thermodynamic parameters and quenching mechanism of the three materials, similarities and differences were determined in their interactions with HSA.Results: The results showed that with an increase in the concentration of the AuNPs with the three different morphologies, the UV-vis absorption peak intensity of the mixed solution increased, but its fluorescence intensity was quenched. This indicates that the three types of AuNPs interact with HSA, and that the interactions between them represent a static quenching process, which is consistent with the conclusions derived from three-dimensional fluorescence experiments. Through variable-temperature fluorescence experiments, the binding constants, number of binding sites, and thermodynamic parameters of the interactions between the three types of AuNPs and HSA were determined. The Gibbs free energy changes were <0, indicating that the reactions of the three types of AuNPs with HSA are spontaneous, resulting in associated matter. Binding constant measurements indicated that the strongest binding took place between the AuNFs and HSA. In addition, the results of fluorescence, CD spectroscopy, and FTIR showed that three different shapes of AuNPs can induce conformational changes in HSA and reduce the α-helix content. Among them, AuNFs have the smallest ability to induce conformational changes.Discussion: According to studies, AuNFs interact more favorably with HSA. This can be used as a reference for the administration of drugs containing AuNPs.

Exploring the interactions of Ti3C2Tx, AgNPs, and Ti3C2Tx/AgNPs with human serum albumin: Insights into conformational changes and biotoxicity reduction

Ag nanoparticles (AgNPs) are toxic and can accumulate in the human body or the environment, resulting in biotoxic effects. Ti3C2Tx, a new class of graphene-like 2D nanomaterials, is used in numerous applications due to its special physicochemical properties. There is great concern about the potential damage that this material may cause to the environment and human health. In this study, the interaction mechanisms of Ti3C2Tx, AgNPs and Ti3C2Tx/AgNPs materials with human serum albumin (HSA) were characterized using multispectral analysis and zeta potential measurements, respectively. The results showed that the effects of the three materials on the conformational changes of HSA were AgNPs > Ti3C2Tx/AgNPs > Ti3C2Tx in order. Hydrogen bonding and electrostatic interaction forces played an important role in the binding process of Ti3C2Tx and its complexes with HSA. Ag nanoparticles have a comparatively high level of biotoxicity and have a more significant effect on the conformational changes of proteins. Ti3C2Tx itself has biocompatibility and a large specific surface area. The biotoxicity of Ti3C2Tx/AgNPs complex is lower than that of AgNPs, indicating that the addition of Ti3C2Tx can reduce the biotoxicity of Ag nanoparticles, and Ti3C2Tx may be used as a carrier substance for Ag nanoparticles, which can reduce the toxicity of AgNPs while giving it unique properties similar to those of Ti3C2Tx, thus improve the biosafety of Ag nanoparticles in the application process.

Probing the Interaction between Isoflucypram Fungicides and Human Serum Albumin: Multiple Spectroscopic and Molecular Modeling Investigations.

To better understand the potential toxicity risks of isoflucypram in humans, The interaction between isoflucypram and HSA (human serum albumin) was studied through molecular docking, molecular dynamics simulations, ultraviolet-visible absorption, fluorescence, synchronous fluorescence, three-dimensional fluorescence, Fourier transform infrared spectroscopies, and circular dichroism spectroscopies. The interaction details were studied using the molecular docking method and molecular dynamics simulation method. The results revealed that the effect of isoflucypram on human serum albumin was mixed (static and dynamic) quenching. Additionally, we were able to obtain important information on the number of binding sites, binding constants, and binding distance. The interaction between isoflucypram and human serum albumin occurred mainly through hydrogen bonds and van der Waals forces. Spectroscopic results showed that isoflucypram caused conformational changes in HSA (human serum albumin), in which the α-helix was transformed into a β-turn, β-sheet, and random coil, causing the HSA structure to loosen. By providing new insights into the mechanism of binding between isoflucypram and human serum albumin, our study has important implications for assessing the potential toxicity risks associated with isoflucypram exposure.

A multispectral study and computer simulation on the interaction of pomalidomide with human serum albumin

Pomalidomide (POM) has been discovered as a new molecular-glue-type degraders in recent years. It is a potent immunomodulatory drug and is used for the treatment of recrudescent and intractable multiple myeloma (MM). The interaction between POM and human serum albumin (HSA) was studied by multiple spectral techniques, molecular docking technique, and molecular dynamics simulation in this research. POM and HSA formed a complex with one binding stoichiometry. Site I was the binding site of POM to HSA and the binding constant was (6.180 ± 0.009) × 103 M−1 (293 K). Based on the thermodynamic results, the binding process was exothermic and spontaneous. Van der Waals forces and H-bonds were the chief driving forces. The conformational changes in HSA induced by POM were reflected in β-turn content increasing and α-helix content reducing. The results of computer simulation were consistent with that of the multiple spectral experiments. In addition, the results of molecular docking indicated π electrons in POM were also vital for the stability of HSA-POM complex. Molecular dynamics simulation showed that Leu198, Lys199 and Trp214 played a contributing role in the binding process, and the fluorescence of HSA quenched by POM might be attributed to the reduction in the accessible surface area values of Trp214. This research is aimed at better understanding the effects of molecular-glue-type degraders on human health, and it is helpful in clinical treatment of MM.

Insight into the Interaction Mechanism of HSA with Aztreonam: A Multispectroscopic and Computational Approach.

Aztreonam is a Gram-negative bacteria-targeting synthetic monobactam antibiotic. Human serum albumin (HSA) plays an important role in the transference of pharmaceuticals, hormones, and fatty acids, along with other compounds, determining their biodistribution and physiological fate. Using several biophysical and in silico approaches, we studied the interaction of aztreonam with HSA under physiological environments in this study. Results confirm the formation of HSA-aztreonam complex where aztreonam showed moderate affinity towards HSA. A static mode of quenching was confirmed from the steady state fluorescence data. FRET findings also showed that there was a significant feasibility of energy transfer between HSA and aztreonam. Site marker displacement experimental conclusion suggested the binding site of aztreonam was the sub-domain IB of HSA. Circular dichroic spectroscopic analysis suggested that aztreonam interaction decreases the α-helical content of HSA. Changes in microenvironment were studied through synchronous fluorescence data. According to molecular docking results, the HSA-aztreonam complex is mostly maintained by non-covalent forces, with a binding energy of 7.7 kcal mol-1. The presence of a hydrogen bond, van der Waal interaction, and pi-anion interaction in the binding process, as well as conformational changes in HSA after binding with aztreonam, are all confirmed by molecular dynamic simulation.

Unravelling Binding of Human Serum Albumin with Galantamine: Spectroscopic, Calorimetric, and Computational Approaches.

Human serum albumin (HSA), an abundant plasma protein, binds to various ligands, acting as a transporter for numerous endogenous and exogenous substances. Galantamine (GAL), an alkaloid, treats cognitive decline in mild to moderate Alzheimer’s disease and other memory impairments. A vital step in pharmacological profiling involves the interaction of plasma protein with the drugs, and this serves as an essential platform for pharmaceutical industry advancements. This study is carried out to understand the binding mechanism of GAL with HSA using computational and experimental approaches. Molecular docking revealed that GAL preferentially occupies Sudlow’s site I, i.e., binds to subdomain IIIA. The results unveiled that GAL binding does not induce any conformational change in HSA and hence does not compromise the functionality of HSA. Molecular dynamics simulation (250 ns) deciphered the stability of the HSA–GAL complex. We performed the fluorescence binding and isothermal titration calorimetry (ITC) to analyze the actual binding of GAL with HSA. The results suggested that GAL binds to HSA with a significant binding affinity. ITC measurements also delineated thermodynamic parameters associated with the binding of GAL to HSA. Altogether, the present study deciphers the binding mechanism of GAL with HSA.

Unveiling interaction mechanisms between myricitrin and human serum albumin: Insights from multi-spectroscopic, molecular docking and molecular dynamic simulation analyses

Myricitrin is a natural polyhydroxy flavonoid and is mainly derived from the bark and leaves of the Chinese Bayberry tree (Myrica rubra). It has different pharmacological activities, including antioxidative, anti-inflammatory, hypoglycemic, antiviral, liver protection and cholagogue properties, and may be added to foods, pharmaceuticals, and cosmetic products for antioxidant purposes. In this study, the interaction mechanism between myricitrin and human serum albumin (HSA) was investigated using spectroscopic methods, molecular docking techniques, and molecular dynamic simulations. We showed that the HSA/myricitrin interaction exhibited a static fluorescence quenching mechanism, and that binding processes were spontaneous in nature, with the main forces exemplified by hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Fluorescence spectroscopy, ultraviolet–visible (UV–vis) spectroscopy, synchronous fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, micro-Fourier transform infrared spectroscopy (micro-FTIR), and circular dichroism (CD) spectroscopy showed that myricitrin binding altered the HSA conformation to some extent. Competitive binding and molecular docking studies showed that the preferred binding of myricitrin on HSA was in the sub-structural domain IIA (Site I); molecular dynamic simulations revealed that myricitrin interacted with HSA to produce a well stabilized complex, and it also generated a conformational change in HSA. The antioxidant capacity of the HSA-myricitrin complex was reduced when compared with free myricitrin. The identification of HSA-myricitrin binding mechanisms provides valuable insights for the application of myricitrin to the food and pharmaceutical industries.

A multi-spectroscopic and computational simulations study to delineate the interaction between antimalarial drug hydroxychloroquine and human serum albumin

Hydroxychloroquine (HCQ), a quinoline based medicine is commonly used to treat malaria and autoimmune diseases such as rheumatoid arthritis. Since, human serum albumin (HSA) serves as excipient for vaccines or therapeutic protein drugs, it is important to understand the effect of HCQ on the structural stability of HSA. In this study, the binding mechanism of HCQ and their effect on stability of HSA have been studied using various spectroscopic techniques and molecular dynamic simulation. The UV-VIS results confirmed the strong binding of HCQ with HSA. The calculated thermodynamics parameters confirmed that binding is spontaneous in nature and van der Waals forces and hydrogen bonding are involved in the binding system which is also confirmed by molecular docking results. The steady-state fluorescence confirms the static quenching mechanism in the interaction system, which was further validated by time-resolved fluorescence. The synchronous fluorescence confirmed the more abrupt binding of HCQ with tryptophan residue of HSA compared to Tyr residue of HSA. Isothermal titration calorimetry (ITC) was done to validate the thermodynamics parameters of HSA-HCQ complex in one experiment, supporting the values obtained from the spectroscopic techniques. The circular dichroism (CD) demonstrated that the HCQ affected the secondary structure of HSA protein by reducing their α-helical content. The docking and molecular dynamic simulation results further helped in understanding the effect of HCQ on conformational changes of HSA. Overall, present work defined the physicochemical properties and interaction mechanism of HCQ with HSA that have extensively been elucidated by both in vitro and in silico approaches. Communicated by Ramaswamy H. Sarma

Human serum albumin adsorption on cellulose nanocrystal: A spectroscopy and molecular dynamics simulation research

Cellulose nanocrystal (CNC) is a relatively new natural nanoparticle derived from plants. Several biomedical applications are envisioned for CNC. Although its safety upon systemic administration is still questionable, it may serve as a worthy substrate for the adsorption of blood proteins in ex vivo settings for diagnostic purposes. The interaction between CNC and Human serum albumin (HSA) may influence both structure and function of other adsorbed proteins on the CNC surface. Herein, molecular dynamics (MD) simulation and circular dichroism spectroscopy (CD) were utilized to study the conformational changes of HSA in the presence and absence of the CNC. The secondary structure study results show that the HSA structure was conserved during the interaction. Fluorescence spectroscopy indicates that the CNC has a quenching property on the intrinsic fluorescence of HSA. Furthermore, increasing CNC concentrations led to a blue shift in the HSA fluorescence emission at 344 nm. The Gibbs free energy demonstrated the HSA and CNC interaction is spontaneous; the MMPBSA outcomes also approved that electrostatic and van der Waals (vdW) interactions were the major forces in the HSA-CNC complex. The results of this study shed light on the adsorption of HSA on CNC and the nature of their interactions.

Chebulinic and chebulagic acid binding with serum proteins: biophysical and molecular docking approach

Chebulinic acid (CHN) and chebulagic acid (CHG) have been known for centuries for their anti-cancer, anti-diabetes, HIV and anti-inflammatory properties. In this study, the interaction of these phytochemicals CHN/CHG, with the two major transport proteins for various drugs, human serum albumin (HSA) and α-1-acid glycoprotein (AGP), was unraveled by using several spectroscopic techniques and computational methods. The binding of CHN/CHG quenches the HSA/AGP fluorescence intensities, and also these phytochemicals are bound strongly to HSA/AGP proteins. An apparent decrease in fluorescence intensities of CHN/CHG-HSA and CHN/CHG-AGP complex showed the static mode of fluorescence quenching. Furthermore, the intrinsic fluorescence and using site-specific markers ibuprofen competing with these molecules, thereby replacing it in the binding site of subdomain IIIA. The computational methods substantiated the experimental findings, revealing that CHN interacted with Lys414A, Glu492A, Glu492A and Lys413A residues of subdomain IIIA of HSA and for CHG showed the interaction with Lys545A and Lys413A residues of subdomain IIIA of HSA. Fluorescence and surface plasmon resonance data unveiled a previously unreported binding event between CHN/CHG and HSA; the determined binding affinities of both compounds were slightly higher for HSA than AGP. A change in functionality of protein confirmed the esterase‐like activity of HSA in the presence of CHG/CHN upon binding with CHG/CHN. Displacement and circular dichroism (CD) experiments analysis showed that the two CHN/CHG and binding specifically to IIIA subdomain on HSA results in the conformational changes in the HSA. Thus, CD revealed a few conformational changes in HSA due to CHN/CHG. The binding of these two phytochemicals to the plasma proteins would give a path to develop new inspired drug molecules for chronic diseases. Communicated by Ramaswamy H. Sarma

Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches

Pazopanib (PAZ), a tyrosine kinase inhibitor, is used to treat advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS). The FDA approved PAZ for RCC in 2009 and for STS in 2012. The antitumor activity of pazopanib, according to the degree of inhibition, shows different results depending on the dose. Renal cell carcinoma is the most sensitive carcinoma to pazopanib, with 77% inhibition at the 10 mg/kg dose. Clinical studies have shown 53% to 65% inhibition in carcinomas such as breast carcinoma, prostate carcinoma, and melanoma. Plasma proteins such as human serum albumin (HSA) have a critical role in transporting and storing bioactive components. This feature of HSA is very important for the development of cancer therapy. Here, we investigated the interaction between PAZ and HSA to evaluate their binding strength, binding types, and conformational change in HSA. We used spectroscopic methods to assess the drug–protein interaction. Fluorescence measurements revealed that the interaction of PAZ with HSA occurred via the static quenching mechanism. The calculated binding number and binding constants were 1.041 and 1.436 × 106 M−1, respectively, at 298.15 K based on fluorescence screening. The high binding constant and calculated Gibbs free energy at different temperatures showed spontaneous and strong binding. Circular dichroism measurements showed that the α-helix structure of HSA was retained as the secondary structure, with a slight reduction in its percentage after adding PAZ. Furthermore, molecular modeling studies suggested that the docking score of PAZ is higher than those of bicalutamide and ibuprofen, the drugs that were chosen as model competitors against PAZ. Accordingly, PAZ was found to replace bicalutamide and ibuprofen on the HSA binding site, which was also confirmed by UV absorption spectroscopy.

Interactions between stipuol enantiomers and human serum albumin

Natural polyacetylenes occur in food and herbal plants, have a wide range of bioactivities, and are recognized as important nutraceuticals. Stipuol is a natural polyacetylene present in the edible plant Panax notoginseng. The present study was aimed to study interactions of rac-stipuol and its enantiomers with human serum albumin (HSA) using multi-spectroscopic, molecular modeling and microscale thermophoresis. Steady-state and time-resolved fluorescence spectra manifest that the fluorescence quenching mechanism is mainly static in type. The bindings of (S)-stipuol, (R)-stipuol, rac-stipuol lead to some microenvironmental and slight conformational changes of HSA. Competitive ligand displacement experiments and molecular modeling studies revealed that stipuol enantiomers bind to HSA at subdomain III (site IIA). The calculated values of Ka and Kd showed that (R)-stipuol had a stronger binding affinity than (S)-stipuol. The results are informative for use of stipuol as a nutraceutical to improve human health.

A study of the interactions between ephedrine and human serum albumin based on spectroscopic, electrochemical and docking assessments

The aim of this study was to explore the efficiency of ephedrine binding to human serum albumin (HSA) as a protein model using spectroscopic, electrochemical, and molecular docking methods. A reduction in UV absorbance at 280 nm of HSA was attributed to the interaction between ephedrine and HSA. The apparent binding constant (Kapp) values at different temperatures were about 104M−1, which showed high affinity of ephedrine for HSA. The calculated negative enthalpy change (ΔH) and entropy change (ΔS) values suggested that the binding process was mainly driven by van der Waals force and hydrogen bonds. The negative value of free energy change (ΔG) indicated that the interaction process was spontaneous. The results of cyclic voltammetry (CV) further confirmed the high affinity of ephedrine for HSA with an association constant of 2.73 ± 0.17 × 104M−1 at room temperature. Furthermore, molecular docking results revealed that ephedrine bound to site I in subdomain IIA via 2 hydrogen bonds with Phenylalanine 211 (Phe211) and Alanine 215 (Ala215) of HSA, and that Arginine 218 (Arg 218), Lysine 199 (Lys 199), and Serine 202 (Ser202) residues became involved in electrostatic interactions with ephedrine. Also, Leucine 198 (Leu198), Phe211, Tryptophan 214 (Trp214), Leu238, and Histidine 242 (His242) residues were responsible for the stability of the complex via hydrophobic interactions. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to investigate the conformational changes of HSA during the interaction of ephedrine and HSA.

The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes.

Thrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance, and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact hemostasis in several ways. A potentially unrecognized route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate, however, trigger a conformational change in HSA that reduces its ability to bind Zn2+, thus increasing the ion’s availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.