Biophysical chemistry最新文献

Receptor modulated assembly and drug induced disassembly of amyloid beta aggregates at asymmetric neuronal model biomembranes

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-31 DOI: 10.1016/j.bpc.2025.107441

Nirod Kumar Sarangi , Subrata Mondal , Tia E. Keyes

Amyloid peptide non-fibrillar oligomers cause neurotoxicity and may contribute to Alzheimer's disease (AD) pathogenesis. Mounting evidence indicates that Aβ_1–42 oligomers disrupt and remodel neuronal membrane, causing neuronal cell death. The involvement of individual neuronal membrane constituents in real-time Aβ_1–42 aggregate assembly is unclear due to complexity of neuronal cell membrane. We used non-Faradaic electrochemical impedance spectroscopy (EIS) to track monomeric Aβ_1–42 peptide binding and aggregation pathways in real-time in asymmetric micropore suspended lipid bilayer membranes with anionic phospholipids and glycosphingolipids. Anionic DOPC:PIP2 pore suspended membrane showed pore-formation within 2 h of incubation, but peptide insertion occurred over 6 h, with an onset time of ∼6–8 h for peptide aggregation at the membrane surface. Among different gangliosides, peptide binding to GM1- and GM3-containing membranes did not result pore development, but receptor mediated peptide aggregation formation caused membrane admittance to decrease within 2 h. In contrast, partial peptide insertion in the membrane surface increases membrane admittance at GD1a and mixed GSL membranes, arresting aggregation. Time-lapsed AFM imaging at asymmetric solid supported lipid bilayers (aSLBs) corroborated EIS findings, capturing pore-formation and receptor mediated peptide assembly routes. Fluorescence lifetime imaging (FLIM) imaging and spatial resolved single-point fluorescence correlation spectroscopy (FCS) at aSLBs revealed membrane-peptide interaction, assembly, and peptide induced membrane reorganization. Treatment with antidepressants fluoxetine and imipramine therapeutics, in synergy, which are cost-effective and capable of crossing the central nervous system (CNS+), resulted in the disassembly of membrane mediated Aβ_1–42 aggregates, but not fibrils. Overall, the data suggests that membrane-mediated aggregate disassembly at the correct timing of AD progression may halt or reverse amyloid assembly through the use of repurposed drugs.

{"title":"Receptor modulated assembly and drug induced disassembly of amyloid beta aggregates at asymmetric neuronal model biomembranes","authors":"Nirod Kumar Sarangi , Subrata Mondal , Tia E. Keyes","doi":"10.1016/j.bpc.2025.107441","DOIUrl":"10.1016/j.bpc.2025.107441","url":null,"abstract":"<div><div>Amyloid peptide non-fibrillar oligomers cause neurotoxicity and may contribute to Alzheimer's disease (AD) pathogenesis. Mounting evidence indicates that Aβ<sub>1–42</sub> oligomers disrupt and remodel neuronal membrane, causing neuronal cell death. The involvement of individual neuronal membrane constituents in real-time Aβ<sub>1–42</sub> aggregate assembly is unclear due to complexity of neuronal cell membrane. We used non-Faradaic electrochemical impedance spectroscopy (EIS) to track monomeric Aβ<sub>1–42</sub> peptide binding and aggregation pathways in real-time in asymmetric micropore suspended lipid bilayer membranes with anionic phospholipids and glycosphingolipids. Anionic DOPC:PIP2 pore suspended membrane showed pore-formation within 2 h of incubation, but peptide insertion occurred over 6 h, with an onset time of ∼6–8 h for peptide aggregation at the membrane surface. Among different gangliosides, peptide binding to GM1- and GM3-containing membranes did not result pore development, but receptor mediated peptide aggregation formation caused membrane admittance to decrease within 2 h. In contrast, partial peptide insertion in the membrane surface increases membrane admittance at GD1a and mixed GSL membranes, arresting aggregation. Time-lapsed AFM imaging at asymmetric solid supported lipid bilayers (aSLBs) corroborated EIS findings, capturing pore-formation and receptor mediated peptide assembly routes. Fluorescence lifetime imaging (FLIM) imaging and spatial resolved single-point fluorescence correlation spectroscopy (FCS) at aSLBs revealed membrane-peptide interaction, assembly, and peptide induced membrane reorganization. Treatment with antidepressants fluoxetine and imipramine therapeutics, in synergy, which are cost-effective and capable of crossing the central nervous system (CNS+), resulted in the disassembly of membrane mediated Aβ<sub>1–42</sub> aggregates, but not fibrils. Overall, the data suggests that membrane-mediated aggregate disassembly at the correct timing of AD progression may halt or reverse amyloid assembly through the use of repurposed drugs.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107441"},"PeriodicalIF":3.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction of Myrsinoic acid a with biomembrane models: Differential effects on DPPC and DPPS properties revealed by surface rheology and vibrational spectroscopy

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-28 DOI: 10.1016/j.bpc.2025.107439

Ana Gabrieli A. dos Santos, Fernando Cassas, Kevin Figueiredo dos Santos, Livia Soman de Medeiros, Thiago André Moura Veiga, Luciano Caseli

This study investigates the interactions of Myrsinoic acid A, a natural compound with reported anti-inflammatory and antitumor properties, with lipid monolayers composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS). Utilizing tensiometry, polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), Brewster Angle Microscopy (BAM), and surface rheology, we analyzed how Myrsinoic acid A affects the structural and mechanical properties of these lipid systems. The PM-IRRAS spectra revealed that Myrsinoic acid A induced disorder in the DPPC monolayer, shifting CH₂ asymmetric stretching peaks and decreasing packing order, while DPPS remained structurally stable. Surface rheology measurements showed reduced elasticity in both lipids, with differential effects on viscosity: a decrease for DPPC and an increase for DPPS, indicating varied molecular interactions. BAM images confirmed that DPPC maintained a homogeneous morphology, while DPPS displayed aggregate formation, suggesting distinct lipid-drug interactions. These findings highlight the importance of lipid composition in modulating the effects of Myrsinoic acid A on membrane properties, providing insights into its potential therapeutic applications in targeting tumorigenic versus non-tumorigenic cells.

{"title":"Interaction of Myrsinoic acid a with biomembrane models: Differential effects on DPPC and DPPS properties revealed by surface rheology and vibrational spectroscopy","authors":"Ana Gabrieli A. dos Santos, Fernando Cassas, Kevin Figueiredo dos Santos, Livia Soman de Medeiros, Thiago André Moura Veiga, Luciano Caseli","doi":"10.1016/j.bpc.2025.107439","DOIUrl":"10.1016/j.bpc.2025.107439","url":null,"abstract":"<div><div>This study investigates the interactions of Myrsinoic acid A, a natural compound with reported anti-inflammatory and antitumor properties, with lipid monolayers composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS). Utilizing tensiometry, polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), Brewster Angle Microscopy (BAM), and surface rheology, we analyzed how Myrsinoic acid A affects the structural and mechanical properties of these lipid systems. The PM-IRRAS spectra revealed that Myrsinoic acid A induced disorder in the DPPC monolayer, shifting CH₂ asymmetric stretching peaks and decreasing packing order, while DPPS remained structurally stable. Surface rheology measurements showed reduced elasticity in both lipids, with differential effects on viscosity: a decrease for DPPC and an increase for DPPS, indicating varied molecular interactions. BAM images confirmed that DPPC maintained a homogeneous morphology, while DPPS displayed aggregate formation, suggesting distinct lipid-drug interactions. These findings highlight the importance of lipid composition in modulating the effects of Myrsinoic acid A on membrane properties, providing insights into its potential therapeutic applications in targeting tumorigenic versus non-tumorigenic cells.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107439"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The amyloidogenic peptide stretch in human tau, tau306–311 is a promising injectable hydrogelator

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-24 DOI: 10.1016/j.bpc.2025.107438

Shubhangini Singh Verma, Shinjini Bhattacharya, Sachin Kumar, Nitin Chaudhary

A vast majority of peptide hydrogelators harbor a bulky, non-native aromatic moiety. Such foreign moieties raise safety concerns as far as biomedical applications of hydrogels are concerned. The hydrogel research, therefore, has branched to another dimension – to identify native or native-like short peptide stretches that could cause the gelation of biological fluids. Using well-defined criteria to identify native peptide stretches that could form a viscous solution in water but cause gelation of phosphate-buffered saline (PBS), we identified the hexapeptide stretch from human tau, viz. tau^306–311, as a promising injectable hydrogelator. The peptide causes instant gelation of PBS and the cell culture media. Such hydrogels find applications as drug delivery vehicles, scaffolds for mammalian cell culture, wound-dressing material, etc.

引用次数: 0

Characterization of metabolism associated with outcomes in severe acute pancreatitis: Insights from serum metabolomic analysis

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-15 DOI: 10.1016/j.bpc.2025.107436

Mohd Adnan Siddiqui , Anamika Singh , Swarnima Pandey , Mohammed Haris Siddiqui , Afzal Azim , Neeraj Sinha

Severe Acute Pancreatitis (SAP) is characterized by an abrupt onset of pancreatic inflammation, which may induce damage to other organs, and is associated with significant morbidity and mortality. Despite the considerable disease burden, specific treatments to stop progression or prevent occurrence are limited. Currently, there is a paucity of comprehensive studies that thoroughly explore metabolic dysregulation in SAP, particularly those that emphasize changes in outcomes. Nuclear magnetic resonance (NMR) based metabolomics coupled with multivariate analysis was applied to serum samples of 20 survivors and 30 non-survivors of SAP to identify metabolic changes linked to different outcomes. The discriminant analysis of serum samples of SAP survivors and non-survivors revealed isoleucine, leucine, valine, arginine, lactate, and 3-hydroxybutyrate as significant metabolites elevated in the non-survivors. These identified metabolites had shown a significant positive correlation with clinical severity scores in the Pearson correlation analysis. Pathway analysis revealed disruptions in amino acid metabolism, driven by protein catabolism to fulfill the patient's energy requirements. This study highlights the importance of metabolomics in unraveling the molecular and physiological mechanisms underlying SAP. These findings offer valuable insights for clinicians to develop treatment strategies that target metabolic pathways in SAP, potentially for improving patient outcomes.

{"title":"Characterization of metabolism associated with outcomes in severe acute pancreatitis: Insights from serum metabolomic analysis","authors":"Mohd Adnan Siddiqui , Anamika Singh , Swarnima Pandey , Mohammed Haris Siddiqui , Afzal Azim , Neeraj Sinha","doi":"10.1016/j.bpc.2025.107436","DOIUrl":"10.1016/j.bpc.2025.107436","url":null,"abstract":"<div><div>Severe Acute Pancreatitis (SAP) is characterized by an abrupt onset of pancreatic inflammation, which may induce damage to other organs, and is associated with significant morbidity and mortality. Despite the considerable disease burden, specific treatments to stop progression or prevent occurrence are limited. Currently, there is a paucity of comprehensive studies that thoroughly explore metabolic dysregulation in SAP, particularly those that emphasize changes in outcomes. Nuclear magnetic resonance (NMR) based metabolomics coupled with multivariate analysis was applied to serum samples of 20 survivors and 30 non-survivors of SAP to identify metabolic changes linked to different outcomes. The discriminant analysis of serum samples of SAP survivors and non-survivors revealed isoleucine, leucine, valine, arginine, lactate, and 3-hydroxybutyrate as significant metabolites elevated in the non-survivors. These identified metabolites had shown a significant positive correlation with clinical severity scores in the Pearson correlation analysis. Pathway analysis revealed disruptions in amino acid metabolism, driven by protein catabolism to fulfill the patient's energy requirements. This study highlights the importance of metabolomics in unraveling the molecular and physiological mechanisms underlying SAP. These findings offer valuable insights for clinicians to develop treatment strategies that target metabolic pathways in SAP, potentially for improving patient outcomes.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107436"},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A detailed review of genetically encodable RFPs and far-RFPs and their applications in advanced super-resolution imaging techniques

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-15 DOI: 10.1016/j.bpc.2025.107432

Jianshu Dong , Bilal Tayyab , Jiangyun Wang

The red fluorescent proteins (RFPs) and far-red fluorescent proteins (far-RFPs) that are encoded genetically can emit fluorescence within the spectral ranges of 580–680 nm when exposed to the light of appropriate wavelengths. Unlike many RFPs derived from coral species, numerous far-RFPs are optimized synthetic constructs engineered from different orange or red-emitting progenitors. Various categories have been established for the available RFPs and far-red fluorescent proteins based on their photo-chemical profile, fluorescence mechanism, and switching kinetics. Fluorescent probes (FPs) derived from these classes are extensively utilized for labelling and visualizing in vivo and in vitro specimens. Traditional optical microscopy methods generate diffraction-limited, indistinct images owing to the restricted resolution capability of light ranging from 200 to 300 nm. Since 2005, super-resolution microscopy has been a topic of great interest due to its ability to achieve imaging at spatial resolutions of less than 100 nm. The 2014 Nobel Prize in Chemistry was awarded to Eric Betzig, Stefan Hell, and William E. Moerner for their contributions to demonstrating the effectiveness of genetically encodable fluorescent proteins in visualizing biological systems through super-resolution fluorescence microscopy. This review provides a concise overview of RFPs and far-RFPs, including the involvement of surrounding residues in chromophore intactness, stability, autocatalytic maturation and switching kinetics. All the chemical pathways proposed for photoactivation, photoconversion and photoswitching mechanisms are concisely reviewed. Subsequently, a comprehensive summary was provided regarding the various types of super-resolution techniques that are commonly employed, elucidating their underlying principles of operation, as well as the potential future applications of RFPs/far-RFPs in the field of biological imaging.

{"title":"A detailed review of genetically encodable RFPs and far-RFPs and their applications in advanced super-resolution imaging techniques","authors":"Jianshu Dong , Bilal Tayyab , Jiangyun Wang","doi":"10.1016/j.bpc.2025.107432","DOIUrl":"10.1016/j.bpc.2025.107432","url":null,"abstract":"<div><div>The red fluorescent proteins (RFPs) and far-red fluorescent proteins (far-RFPs) that are encoded genetically can emit fluorescence within the spectral ranges of 580–680 nm when exposed to the light of appropriate wavelengths. Unlike many RFPs derived from coral species, numerous far-RFPs are optimized synthetic constructs engineered from different orange or red-emitting progenitors. Various categories have been established for the available RFPs and far-red fluorescent proteins based on their photo-chemical profile, fluorescence mechanism, and switching kinetics. Fluorescent probes (FPs) derived from these classes are extensively utilized for labelling and visualizing in vivo and in vitro specimens. Traditional optical microscopy methods generate diffraction-limited, indistinct images owing to the restricted resolution capability of light ranging from 200 to 300 nm. Since 2005, super-resolution microscopy has been a topic of great interest due to its ability to achieve imaging at spatial resolutions of less than 100 nm. The 2014 Nobel Prize in Chemistry was awarded to Eric Betzig, Stefan Hell, and William E. Moerner for their contributions to demonstrating the effectiveness of genetically encodable fluorescent proteins in visualizing biological systems through super-resolution fluorescence microscopy. This review provides a concise overview of RFPs and far-RFPs, including the involvement of surrounding residues in chromophore intactness, stability, autocatalytic maturation and switching kinetics. All the chemical pathways proposed for photoactivation, photoconversion and photoswitching mechanisms are concisely reviewed. Subsequently, a comprehensive summary was provided regarding the various types of super-resolution techniques that are commonly employed, elucidating their underlying principles of operation, as well as the potential future applications of RFPs/far-RFPs in the field of biological imaging.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107432"},"PeriodicalIF":3.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction of native and aggregated albumin with DMPC bilayers

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-14 DOI: 10.1016/j.bpc.2025.107431

Brigitte Magdalena Merino , Rosa Bartucci , Rita Guzzi

The study of protein-lipid interaction offers interesting insights into the mutual alterations determined in the formation of the supramolecular complex. It gains even more interest, not only in basic research but also in biomedical and biomaterial applications, when protein aggregation and fibril formation are involved. In this study, the reciprocal influence of human serum albumin (HSA), in both the native and the thermally aggregated state, and dimyristoylphosphatidylcholine (DMPC) bilayers is investigated by combining UV–Vis scattering, attenuated total reflection Fourier transform infrared (ATR-FTIR), and spin-label electron paramagnetic resonance (EPR) spectroscopies. Temperature-dependent optical density at fixed wavelength reveals the pre- and the main phase transitions in DMPC bilayers as well as the onset of protein aggregation at T_agg ≈ 70 °C. In native protein/lipid complexes, the protein adsorption on the membrane surfaces suppresses the pre-transition and downshifts the temperature of the main phase transitions of DMPC, whereas the presence of DMPC increases T_agg without affecting the thermal profile. Kinetics experiments reveal that lipid bilayers reduce the thermally-induced aggregation of the protein. ATR-FTIR data indicate that albumin weakens the hydrogen bonding network at the carbonyl groups of the membrane. Conversely, lipid bilayers in any physical state do not alter the structural features of both native and aggregated HSA. In protein/lipid complexes, spin-label EPR of the lipid component reveals that the proteins reduce the packing density of the first chain segments and stabilize the fluid state, the effect being more evident for the native protein.

{"title":"Interaction of native and aggregated albumin with DMPC bilayers","authors":"Brigitte Magdalena Merino , Rosa Bartucci , Rita Guzzi","doi":"10.1016/j.bpc.2025.107431","DOIUrl":"10.1016/j.bpc.2025.107431","url":null,"abstract":"<div><div>The study of protein-lipid interaction offers interesting insights into the mutual alterations determined in the formation of the supramolecular complex. It gains even more interest, not only in basic research but also in biomedical and biomaterial applications, when protein aggregation and fibril formation are involved. In this study, the reciprocal influence of human serum albumin (HSA), in both the native and the thermally aggregated state, and dimyristoylphosphatidylcholine (DMPC) bilayers is investigated by combining UV–Vis scattering, attenuated total reflection Fourier transform infrared (ATR-FTIR), and spin-label electron paramagnetic resonance (EPR) spectroscopies. Temperature-dependent optical density at fixed wavelength reveals the pre- and the main phase transitions in DMPC bilayers as well as the onset of protein aggregation at T<sub>agg</sub> ≈ 70 °C. In native protein/lipid complexes, the protein adsorption on the membrane surfaces suppresses the pre-transition and downshifts the temperature of the main phase transitions of DMPC, whereas the presence of DMPC increases T<sub>agg</sub> without affecting the thermal profile. Kinetics experiments reveal that lipid bilayers reduce the thermally-induced aggregation of the protein. ATR-FTIR data indicate that albumin weakens the hydrogen bonding network at the carbonyl groups of the membrane. Conversely, lipid bilayers in any physical state do not alter the structural features of both native and aggregated HSA. In protein/lipid complexes, spin-label EPR of the lipid component reveals that the proteins reduce the packing density of the first chain segments and stabilize the fluid state, the effect being more evident for the native protein.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107431"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the interaction of an imidazo-pyrimidine derivative with serum proteins: Spectroscopic, computational and structure-activity relationship analysis

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-13 DOI: 10.1016/j.bpc.2025.107435

Bishwayan Chakraborty , Asmit Santra , Debangana Tah , Koushik Goswami , Anupam Jana , Agnishwar Girigoswami , Debosreeta Bose

In the present article, we have tried to theoretically analyze the structure-function relationship of a novel imidazo pyrimidine derivative, IPD, and decipher its interactions with two serum proteins, BSA and HSA, spectroscopically. IPD is almost non-fluorescent in a polar environment, but its fluorescence enhancement is significant in non-polar mediums like proteins. Steady-state fluorometric investigations indicate a strong binding interaction between the probe, IPD, and serum proteins, with HSA being more strongly bound to IPD. This stronger binding affinity of the IPD–HSA complex than compared to the IPD–BSA complex was corroborated through denaturation and quenching studies, too. In silico molecular docking interactions also reveal a similar stronger binding affinity in HSA than BSA. This is attributed to the probe residing in a more hydrophobic region in HSA; thus, the π and alkyl interactions are stronger in HSA than in BSA.

{"title":"Decoding the interaction of an imidazo-pyrimidine derivative with serum proteins: Spectroscopic, computational and structure-activity relationship analysis","authors":"Bishwayan Chakraborty , Asmit Santra , Debangana Tah , Koushik Goswami , Anupam Jana , Agnishwar Girigoswami , Debosreeta Bose","doi":"10.1016/j.bpc.2025.107435","DOIUrl":"10.1016/j.bpc.2025.107435","url":null,"abstract":"<div><div>In the present article, we have tried to theoretically analyze the structure-function relationship of a novel imidazo pyrimidine derivative, IPD, and decipher its interactions with two serum proteins, BSA and HSA, spectroscopically. IPD is almost non-fluorescent in a polar environment, but its fluorescence enhancement is significant in non-polar mediums like proteins. Steady-state fluorometric investigations indicate a strong binding interaction between the probe, IPD, and serum proteins, with HSA being more strongly bound to IPD. This stronger binding affinity of the IPD–HSA complex than compared to the IPD–BSA complex was corroborated through denaturation and quenching studies, too. In silico molecular docking interactions also reveal a similar stronger binding affinity in HSA than BSA. This is attributed to the probe residing in a more hydrophobic region in HSA; thus, the π and alkyl interactions are stronger in HSA than in BSA.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107435"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Equilibrium solubility, solvent effect, solvation and thermodynamic modeling of 1, 3-dinitropyrazole in solutions of methyl alcohol /ethyl alcohol + water

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-10 DOI: 10.1016/j.bpc.2025.107430

Adel Noubigh , Manef Abderrabba

1,3-dinitropyrazole's (DNP) solubility was studied by utilizing the gravimetric method across temperatures ranging 278.15 to 318.15 K and a pressure of 101.2 kPa. In the study, two solvent mixtures were investigated: aqueous methyl alcohol and aqueous ethyl alcohol. Based on the findings, higher temperatures favorably influenced solute dissolution in both solvent systems. To relate the solubility of DNP in two binary solvents mixture, the KAT-LSER model was used. This implies that the polarity of the solvents, as well as the cavity term and hydrogen bonding interactions were pivotal to DNP's solubility. By utilizing the Jouyban-Acree, van't Hoff-Jouyban-Acree, Apelblat-Jouyban-Acree and Ma models, the derived results were compiled. The experimental results prove that the Apelblat-Jouyban-Acree model could give the best correlation results with the experimental data, with the overall relative average deviation values (RAD) of 2.05 %, 2.51 % and the root mean-square deviation (RMSD) of 0.415 × 10⁻⁴, 0.492 × 10⁻⁴ in aqueous methyl alcohol and aqueous ethyl alcohol, respectively. Using the inverse Kirkwood–Buff integrals method, the preferential solvation parameters for the solute DNP determined. The obtained results show that DNP exhibited a preference for solvation in methyl alcohol and ethyl alcohol at all mole fractions of alcohol.

{"title":"Equilibrium solubility, solvent effect, solvation and thermodynamic modeling of 1, 3-dinitropyrazole in solutions of methyl alcohol /ethyl alcohol + water","authors":"Adel Noubigh , Manef Abderrabba","doi":"10.1016/j.bpc.2025.107430","DOIUrl":"10.1016/j.bpc.2025.107430","url":null,"abstract":"<div><div>1,3-dinitropyrazole's (DNP) solubility was studied by utilizing the gravimetric method across temperatures ranging 278.15 to 318.15 K and a pressure of 101.2 kPa. In the study, two solvent mixtures were investigated: aqueous methyl alcohol and aqueous ethyl alcohol. Based on the findings, higher temperatures favorably influenced solute dissolution in both solvent systems. To relate the solubility of DNP in two binary solvents mixture, the KAT-LSER model was used. This implies that the polarity of the solvents, as well as the cavity term and hydrogen bonding interactions were pivotal to DNP's solubility. By utilizing the Jouyban-Acree, van't Hoff-Jouyban-Acree, Apelblat-Jouyban-Acree and Ma models, the derived results were compiled. The experimental results prove that the Apelblat-Jouyban-Acree model could give the best correlation results with the experimental data, with the overall relative average deviation values (RAD) of 2.05 %, 2.51 % and the root mean-square deviation (RMSD) of 0.415 × 10<sup>−4</sup>, 0.492 × 10<sup>−4</sup> in aqueous methyl alcohol and aqueous ethyl alcohol, respectively. Using the inverse Kirkwood–Buff integrals method, the preferential solvation parameters for the solute DNP determined. The obtained results show that DNP exhibited a preference for solvation in methyl alcohol and ethyl alcohol at all mole fractions of alcohol.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"322 ","pages":"Article 107430"},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autoencoder-based drug-virus association prediction with reliable negative sample selection: A case study with COVID-19

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-10 DOI: 10.1016/j.bpc.2025.107434

A.S. Aruna , K.R. Remesh Babu , K. Deepthi

Emergence of viruses cause unprecedented challenges and thus leading to wide-ranging consequences today. The world has faced massive disruptions like COVID-19 and continues to suffer in terms of public health and world economy. Fighting with this emergence of viruses and its reemergence plays a critical role in the health care industry. Identification of novel virus-drug associations is a vital step in drug discovery. Prediction and prioritization of novel virus-drug associations through computational approaches is an alternative and best choice considering the cost and risk of biological experiments. This study proposes a method, KR-AEVDA that relies on k-nearest neighbor based reliable negative sample selection and autoencoder based feature extraction to explore promising virus-drug associations for further experimental validation. The method analyzes complex relationships among drugs and viruses by investigating similarity and association data between drugs and viruses. It generates feature vectors from the similarity data, and reliable negative samples are extracted through an effective distance-based algorithm from the unlabeled samples in the dataset. Then high level features are extracted via an autoencoder and is fed to an ensemble classifier for inferring novel associations. Experimental results on three different datasets showed that KR-AEVDA reliably attained better performance than other state-of-the-art methods. Molecular docking is carried out between the top-predicted drugs and the crystal structure of the SARS-CoV-2's main protease to further validate the predictions. Case studies for SARS-CoV-2 illustrate the effectiveness of KR-AEVDA in identifying potential virus-drug associations.

病毒的出现带来了前所未有的挑战，从而导致了今天广泛的后果。世界已经面临了像 COVID-19 这样的大规模破坏，在公共卫生和世界经济方面继续遭受损失。应对这种病毒的出现和再次出现在医疗保健行业中起着至关重要的作用。鉴定新型病毒与药物的关联是药物发现的重要一步。考虑到生物实验的成本和风险，通过计算方法预测新型病毒与药物的关联并确定其优先次序是一种可供选择的最佳方法。本研究提出了一种名为 KR-AEVDA 的方法，它依赖于基于 k 近邻的可靠负样本选择和基于自动编码器的特征提取来探索有前景的病毒-药物关联，以便进一步进行实验验证。该方法通过研究药物和病毒之间的相似性和关联数据，分析药物和病毒之间的复杂关系。它从相似性数据中生成特征向量，并通过有效的基于距离的算法从数据集中的未标记样本中提取可靠的阴性样本。然后通过自动编码器提取高级特征，并将其输入集合分类器以推断新的关联。在三个不同数据集上的实验结果表明，KR-AEVDA 能可靠地获得比其他先进方法更好的性能。为了进一步验证预测结果，KR-AEVDA 将预测结果最好的药物与 SARS-CoV-2 主要蛋白酶的晶体结构进行了分子对接。针对 SARS-CoV-2 的案例研究说明了 KR-AEVDA 在识别潜在病毒-药物关联方面的有效性。

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引用次数: 0

Relevance of ceramide 1-phosphate domain formation in activation of cytosolic phospholipase A2

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry

Pub Date : 2025-03-09 DOI: 10.1016/j.bpc.2025.107433

Tomokazu Yasuda , Daiki Ueura , Madoka Nakagomi , Shinya Hanashima , Michio Murata

Ceramide 1-phosphate (C1P), as a lipid mediator, specifically binds and activates cytosolic phospholipase A₂α (cPLA₂α). Previous findings revealed that modification of the specific hydrophobic moiety decreases the affinity with cPLA₂α. However, the possible biological role of the temporal C1P-enriched domains formed in biomembranes for the molecular recognition of cPLA₂α has not been fully elucidated. In this study we elucidated the properties of segregated domains formed by C1P (and its analogs) and the affinity of cPLA₂α for C1P in different co-lipid environments by fluorescence spectroscopy using trans-parinaric acid and surface plasmon resonance (SPR). Fluorescence measurements suggested that the formation of C1P ordered domains is strongly influenced by interfacial 3-OH and phosphate groups of C1P, such as hydrogen-bonding and electrostatic interactions, and depends on the co-lipid composition of the host bilayer. SPR indicated that C1P under the lipid environment favorable for the formation of C1P clusters has higher affinity for cPLA₂α. Thus, we speculate that C1P clusters formed under certain membrane conditions are important in specific binding with cPLA₂α by increasing the interaction between the C1P headgroup and basic residues of cPLA₂α. In conclusion, this study revealed that the local formation of lipid mediator-rich clusters in biomembranes likely has a significant effect on the interaction between the mediator and its receptor protein.

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引用次数: 0