European Biophysics Journal最新文献_第4页

Computational discovery of dual potential inhibitors of SARS‐CoV‐2 spike/ACE2 and Mpro: 3D-pharmacophore, docking-based virtual screening, quantum mechanics and molecular dynamics 通过计算发现 SARS-CoV-2 spike/ACE2 和 Mpro 的双重潜在抑制剂：三维药性、基于对接的虚拟筛选、量子力学和分子动力学。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-06-21 DOI: 10.1007/s00249-024-01713-z

Boris D. Bekono, Pascal Amoa Onguéné, Conrad V. Simoben, Luc C. O. Owono, Fidele Ntie-Kang

{"title":"Computational discovery of dual potential inhibitors of SARS‐CoV‐2 spike/ACE2 and Mpro: 3D-pharmacophore, docking-based virtual screening, quantum mechanics and molecular dynamics","authors":"Boris D. Bekono, Pascal Amoa Onguéné, Conrad V. Simoben, Luc C. O. Owono, Fidele Ntie-Kang","doi":"10.1007/s00249-024-01713-z","DOIUrl":"10.1007/s00249-024-01713-z","url":null,"abstract":"<div><p>To find drugs against COVID-19, caused by the SARS-CoV-2, promising targets include the fusion of the viral spike with the human angiotensin-converting enzyme 2 (ACE2) as well as the main protease (M<sup>pro</sup>). These proteins are responsible for viral entry and replication, respectively. We combined several state-of-the-art computational methods, including, protein–ligand interaction fingerprint, 3D-pharmacophores, molecular-docking, MM-GBSA, DFT, and MD simulations to explore two databases: ChEMBL and NANPDB to identify molecules that could both block spike/ACE2 fusion and inhibit M<sup>pro</sup>. A total of 1,690,649 compounds from the two databases were screened using the pharmacophore model obtained from PLIF analysis. Five recent complexes of M<sup>pro</sup> co-crystallized with different ligands were used to generate the pharmacophore model, allowing 4,829 compounds that passed this prefilter. These were then submitted to molecular docking against M<sup>pro</sup>. The 5% top-ranked docking hits from docking result having scores <span>(<)</span> −8.32 kcal mol<sup>−1</sup> were selected and then docked against spike/ACE2. Only four compounds: ChEMBL244958, ChEMBL266531, ChEMBL3680003, and 1-methoxy-3-indolymethyl glucosinolate (<b>4</b>) displayed binding energies <span>(<-)</span> 8.21 kcal mol<sup>−1</sup> (for the native ligand) were considered as putative dual-target inhibitors. Furthermore, predictive ADMET, MM-GBSA and DFT/6-311G(d,p) were performed on these compounds and compared with those of well-known antivirals. DFT calculations showed that ChEMBL244958 and compound <b>4</b> had significant predicted reactivity values. Molecular dynamics simulations of the docked complexes were run for 100 ns and used to validate the stability docked poses and to confirm that these hits are putative dual binders of the spike/ACE2 and the M<sup>pro</sup>.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 5-6","pages":"277 - 298"},"PeriodicalIF":2.2,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 conformational properties of alamethicin in ethanol studied by NMR 用核磁共振法研究乙醇中阿拉米嗪的构象特性。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-06-08 DOI: 10.1007/s00249-024-01711-1

Yoshinori Miura

{"title":"The conformational properties of alamethicin in ethanol studied by NMR","authors":"Yoshinori Miura","doi":"10.1007/s00249-024-01711-1","DOIUrl":"10.1007/s00249-024-01711-1","url":null,"abstract":"<div><p>Alamethicin, a peptide consisted of 20 amino acid residues, has been known to function as an antibiotic. The peptides self-associate in biological membranes, form an ion channel, and then induce cell death by leaking intracellular contents through a transmembrane pore of an ion channel. We investigated conformation and its thermal stability of alamethicin-A6 and -U6 in ethanol using proton nuclear magnetic resonance (NMR) spectroscopy; alamethicin-A6 and -U6 have the amino acid sequences of UPUAU<u>A</u>QUVUGLUPVUUQQO and UPUAU<u>U</u>QUVUGLUPVUUQQO, respectively, where U and O represent α-aminoisobutyric acid and phenylalaninol, respectively. As indicated by the under bars in the sequences, only the residue 6 differs between the alamethicins. We show that the alamethicins in ethanol form helix conformation in the region of the residues 2–11 and a non-regular conformation in the regions of the N- and C-termini, and that the helices are maintained up to 66 °C at least. Conformations in the region of the residues 12–18 of the alamethicins, however, are not well identified due to the lack of NMR data. In addition, we demonstrate that the amide proton chemical shift temperature coefficients’ method, which is known as an indicator for intramolecular hydrogen bonds in peptides and proteins in aqueous solutions, can be also applied to the alamethicins in ethanol. Further, we show that the conformation around the C-terminus of alamethicin-A6 is restrained by intramolecular hydrogen bonds, whereas that of alamethicin-U6 is either restrained or unrestrained by intramolecular hydrogen bonds; the alamethicin-U6 molecules having the restrained and unrestrained conformations coexist in ethanol. We discuss the two types of conformations using a model chain consisting of particles linked by rigid bonds called as the free jointed chain.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 5-6","pages":"267 - 276"},"PeriodicalIF":2.2,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

An obituary: Dr. Helmut Cölfen 1965–2023 讣告赫尔穆特-科尔芬博士 1965-2023。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-06-07 DOI: 10.1007/s00249-024-01712-0

Borries Demeler, Denis Gebauer, Emre Brookes, Jeffrey Fagan, Johannes Walter, José García de la Torre, Juan Manuel García-Ruiz, Kristian Schilling, Mengdi Chen, Lukas Dobler, Olwyn Byron, Stephen E. Harding, Thomas Zemb, Tobias Kraus, Tom Laue, Trushar R. Patel

{"title":"An obituary: Dr. Helmut Cölfen 1965–2023","authors":"Borries Demeler, Denis Gebauer, Emre Brookes, Jeffrey Fagan, Johannes Walter, José García de la Torre, Juan Manuel García-Ruiz, Kristian Schilling, Mengdi Chen, Lukas Dobler, Olwyn Byron, Stephen E. Harding, Thomas Zemb, Tobias Kraus, Tom Laue, Trushar R. Patel","doi":"10.1007/s00249-024-01712-0","DOIUrl":"10.1007/s00249-024-01712-0","url":null,"abstract":"<div><p>Dr. Helmut Cölfen, an exceptional interdisciplinary scientist, mentor, colleague, and dear friend, passed away in November 2023 at the age of 58. His untimely departure is a profound loss for the fields of analytical ultracentrifugation, colloid, crystallization, and polymer research. This obituary pays tribute to Helmut, honoring his remarkable academic career and contributions to the study of nanochemistry, biophysics, and life sciences. Helmut was renowned for his pioneering research contributions in several key research areas: (1) Development of advanced analytical techniques: Helmut made major contributions to techniques such as analytical ultracentrifugation and field flow fractionation, which are widely utilized to characterize the structure of biomolecules and the growth of nanostructured crystalline materials; (2) Study of nucleation and crystallization processes: Helmut explored the early stages of crystallization which led to the discovery of pre-nucleation clusters and mesocrystal intermediates, in the presence of additives and templates; and (3) Investigation of structure and morphogenesis of mesocrystals, examining their molecular properties.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 5-6","pages":"249 - 254"},"PeriodicalIF":2.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Two-layer elastic models for single-yeast compressibility with flat microlevers 带平面微杠杆的单酵母可压缩性双层弹性模型

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-05-04 DOI: 10.1007/s00249-024-01710-2

L. Delmarre, E. Harté, A. Devin, P. Argoul, F. Argoul

{"title":"Two-layer elastic models for single-yeast compressibility with flat microlevers","authors":"L. Delmarre, E. Harté, A. Devin, P. Argoul, F. Argoul","doi":"10.1007/s00249-024-01710-2","DOIUrl":"10.1007/s00249-024-01710-2","url":null,"abstract":"<div><p>Unicellular organisms such as yeast can survive in very different environments, thanks to a polysaccharide wall that reinforces their extracellular membrane. This wall is not a static structure, as it is expected to be dynamically remodeled according to growth stage, division cycle, environmental osmotic pressure and ageing. It is therefore of great interest to study the mechanics of these organisms, but they are more difficult to study than other mammalian cells, in particular because of their small size (radius of a few microns) and their lack of an adhesion machinery. Using flat cantilevers, we perform compression experiments on single yeast cells (<i>S. cerevisiae</i>) on poly-L-lysine-coated grooved glass plates, in the limit of small deformation using an atomic force microscope (AFM). Thanks to a careful decomposition of force–displacement curves, we extract local scaling exponents that highlight the non-stationary characteristic of the yeast behavior upon compression. Our multi-scale nonlinear analysis of the AFM force-displacement curves provides evidence for non-stationary scaling laws. We propose to model these phenomena based on a two-component elastic system, where each layer follows a different scaling law..</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 4","pages":"205 - 224"},"PeriodicalIF":2.2,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 effect of ionic redistributions on the microwave dielectric response of cytosol water upon glucose uptake 葡萄糖摄取时离子再分布对细胞膜水微波介电响应的影响

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-04-22 DOI: 10.1007/s00249-024-01708-w

Cindy Galindo, Leonid Livshits, Lama Tarabeih, Gregory Barshtein, Sharon Einav, Yuri Feldman

{"title":"The effect of ionic redistributions on the microwave dielectric response of cytosol water upon glucose uptake","authors":"Cindy Galindo, Leonid Livshits, Lama Tarabeih, Gregory Barshtein, Sharon Einav, Yuri Feldman","doi":"10.1007/s00249-024-01708-w","DOIUrl":"10.1007/s00249-024-01708-w","url":null,"abstract":"<div><p>The sensitivity of cytosol water's microwave dielectric (MD) response to D-glucose uptake in Red Blood Cells (RBCs) allows the detailed study of cellular mechanisms as a function of controlled exposures to glucose and other related analytes like electrolytes. However, the underlying mechanism behind the sensitivity to glucose exposure remains a topic of debate. In this research, we utilize MDS within the frequency range of 0.5–40 GHz to explore how ionic redistributions within the cell impact the microwave dielectric characteristics associated with D-glucose uptake in RBC suspensions. Specifically, we compare glucose uptake in RBCs exposed to the physiological concentration of Ca<sup>2+</sup> vs. Ca-free conditions. We also investigate the potential involvement of Na<sup>+</sup>/K<sup>+</sup> redistribution in glucose-mediated dielectric response by studying RBCs treated with a specific Na<sup>+</sup>/K<sup>+</sup> pump inhibitor, ouabain. We present some insights into the MD response of cytosol water when exposed to Ca<sup>2+</sup> in the absence of D-glucose. The findings from this study confirm that ion-induced alterations in bound/bulk water balance do not affect the MD response of cytosol water during glucose uptake.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 4","pages":"183 - 192"},"PeriodicalIF":2.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Site-directed mutagenesis at the Glu78 in Ec-NhaA transporter impacting ion exchange: a biophysical study 影响离子交换的 Ec-NhaA 转运体 Glu78 的定点突变：一项生物物理研究

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-04-22 DOI: 10.1007/s00249-024-01709-9

Anuradha Yadav, Dinesh Kumar, Manish Dwivedi

{"title":"Site-directed mutagenesis at the Glu78 in Ec-NhaA transporter impacting ion exchange: a biophysical study","authors":"Anuradha Yadav, Dinesh Kumar, Manish Dwivedi","doi":"10.1007/s00249-024-01709-9","DOIUrl":"10.1007/s00249-024-01709-9","url":null,"abstract":"<div><p>Na<sup>+</sup>/H<sup>+</sup> antiporters facilitate the exchange of Na<sup>+</sup> for H<sup>+</sup> across the cytoplasmic membrane in prokaryotic and eukaryotic cells. These transporters are crucial to maintain the homeostasis of sodium ions, consequently pH, and volume of the cells. Therefore, sodium/proton antiporters are considered promising therapeutic targets in humans. The Na<sup>+</sup>/H<sup>+</sup> antiporter in <i>Escherichia coli</i> (<i>Ec</i>-NhaA), a prototype of cation–proton antiporter (CPA) family, transports two protons and one sodium (or Li<sup>+</sup>) in opposite direction. Previous mutagenesis experiments on Ec-NhaA have proposed Asp164, Asp163, and Asp133 amino acids with the significant implication in functional and structural integrity and create site for ion-binding. However, the mechanism and the sites for the binding of the two protons remain unknown and controversial which could be critical for pH regulation. In this study, we have explored the role of Glu78 in the regulation of pH by <i>Ec</i>-NhaA. Although we have created various mutants, E78C has shown a considerable effect on the stoichiometry of NhaA and presented comparable phenotypes. The ITC experiment has shown the binding of ~ 5 protons in response to the transport of one lithium ion. The phenotype analysis on selective medium showed a significant expression compared to WT <i>Ec</i>-NhaA. This represents the importance of Glu78 in transporting the H<sup>+</sup> across the membrane where a single mutation with Cys amino acid alters the number of H<sup>+</sup> significantly maintaining the activity of the protein.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 4","pages":"193 - 203"},"PeriodicalIF":2.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Erythrocytes membrane fluidity changes induced by adenylyl cyclase cascade activation: study using fluorescence recovery after photobleaching 腺苷酸环化酶级联激活诱导的红细胞膜流动性变化：利用光漂白后荧光恢复进行的研究

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-04-16 DOI: 10.1007/s00249-024-01707-x

A. N. Semenov, A. E. Lugovtsov, S. A. Rodionov, Eu. G. Maksimov, A. V. Priezzhev, E. A. Shirshin

{"title":"Erythrocytes membrane fluidity changes induced by adenylyl cyclase cascade activation: study using fluorescence recovery after photobleaching","authors":"A. N. Semenov, A. E. Lugovtsov, S. A. Rodionov, Eu. G. Maksimov, A. V. Priezzhev, E. A. Shirshin","doi":"10.1007/s00249-024-01707-x","DOIUrl":"10.1007/s00249-024-01707-x","url":null,"abstract":"<div><p>In this study, fluorescence recovery after photobleaching (FRAP) experiments were performed on RBC labeled by lipophilic fluorescent dye CM-DiI to evaluate the role of adenylyl cyclase cascade activation in changes of lateral diffusion of erythrocytes membrane lipids. Stimulation of adrenergic receptors with epinephrine (adrenaline) or metaproterenol led to the significant acceleration of the FRAP recovery, thus indicating an elevated membrane fluidity. The effect of the stimulation of protein kinase A with membrane-permeable analog of cAMP followed the same trend but was less significant. The observed effects are assumed to be driven by increased mobility of phospholipids resulting from the weakened interaction between the intermembrane proteins and RBC cytoskeleton due to activation of adenylyl cyclase signaling cascade.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 4","pages":"239 - 247"},"PeriodicalIF":2.2,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01707-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Reaction of KHP with excess NaOH or TRIS as standard reactions for calibration of titration calorimeters from 0 to 60 °C 将 KHP 与过量 NaOH 或 TRIS 反应作为校准 0 至 60 °C 滴定热量计的标准反应

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-04-13 DOI: 10.1007/s00249-024-01705-z

Jason D. Kenealey, Margarida Bastos, Zaid Assaf, Guangyue Bai, Wenqi Zhao, Tyler Jarrard, Colter Tower, Lee D. Hansen

{"title":"Reaction of KHP with excess NaOH or TRIS as standard reactions for calibration of titration calorimeters from 0 to 60 °C","authors":"Jason D. Kenealey, Margarida Bastos, Zaid Assaf, Guangyue Bai, Wenqi Zhao, Tyler Jarrard, Colter Tower, Lee D. Hansen","doi":"10.1007/s00249-024-01705-z","DOIUrl":"10.1007/s00249-024-01705-z","url":null,"abstract":"<div><p>Calibration of titration calorimeters is an ongoing problem, particularly with calorimeters with reaction vessel volumes < 10 mL in which an electrical calibration heater is positioned outside the calorimetric vessel. Consequently, a chemical reaction with a known enthalpy change must be used to accurately calibrate these calorimeters. This work proposes the use of standard solutions of potassium acid phthalate (KHP) titrated into solutions of excess sodium hydroxide (NaOH) or excess tris(hydroxymethyl)aminomethane (TRIS) as standard reactions to determine the collective accuracy of the relevant variables in a determination of the molar enthalpy change for a reaction. KHP is readily available in high purity, weighable for easy preparation of solutions with accurately known concentrations, stable in solution, not compromised by side reactions with common contaminants such as atmospheric CO<sub>2</sub>, and non-corrosive to materials used in calorimeter construction. Molar enthalpy changes for these reactions were calculated from 0 to 60 °C from reliable literature data for the p<i>K</i><sub>a</sub> of KHP, the molar enthalpy change for protonation of TRIS, and the molar enthalpy change for ionization of water. The feasibility of using these reactions as enthalpic standards was tested in several calorimeters; a 50 mL CSC 4300, a 185 μL NanoITC, a 1.4 mL VP-ITC, and a TAM III with 1 mL reaction vessels. The results from the 50 mL CSC 4300, which was accurately calibrated with an electric heater, verified the accuracy of the calculated standard values for the molar enthalpy changes of the proposed reactions.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 4","pages":"225 - 238"},"PeriodicalIF":2.2,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01705-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Application of electron paramagnetic resonance spectroscopy for determining the relative nanoenvironment fluidity of polymeric micelles 应用电子顺磁共振波谱测定聚合物胶束的相对纳米环境流动性

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-04-10 DOI: 10.1007/s00249-024-01706-y

Lusine Tonoyan, Sirazum Munira, Afsaneh Lavasanifar, Arno G. Siraki

{"title":"Application of electron paramagnetic resonance spectroscopy for determining the relative nanoenvironment fluidity of polymeric micelles","authors":"Lusine Tonoyan, Sirazum Munira, Afsaneh Lavasanifar, Arno G. Siraki","doi":"10.1007/s00249-024-01706-y","DOIUrl":"10.1007/s00249-024-01706-y","url":null,"abstract":"<p>Polymeric micelles are nanocarriers for drug, protein and gene delivery due to their unique core/shell structure, which encapsulates and protects therapeutic cargos with diverse physicochemical properties. However, information regarding the micellar nanoenvironment's fluidity can provide unique insight into their makeup. In this study, we used electron paramagnetic resonance (EPR) spectroscopy to study free radical spin probe (5-doxylstearate methyl ester, 5-MDS, and 16-doxylstearic acid, 16-DS) behaviour in methoxy-poly(ethylene oxide)-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-PBCL) and methoxy-poly(ethylene oxide)-poly(ε-caprolactone) (PEO-PCL) polymeric micelles. Spin probes provided information about the spectroscopic rotational correlation time (τ, s) and the spectroscopic partition parameter F. We hypothesized that spin probes would partition into the polymeric micelles, and these parameters would be calculated. The results showed that both 5-MDS and 16-DS spectra were modulated in the presence of polymeric micelles. Based on τ values, 5-MDS revealed that PEO-PCL (τ = 3.92 ± 0.26 × 10<sup>−8</sup> s) was more fluid than PEO-PBCL (τ = 7.15 ± 0.63 × 10<sup>−8</sup> s). The F parameter, however, could not be calculated due to the rotational hindrance of the probe within the micelles. With 16-DS, more probe rotation was observed, and although the F parameter could be calculated, it was not helpful to distinguish the micelles' fluidity. Also, doxorubicin-loading interfered with the spin probes, particularly for 16-DS. However, using simulations, we could distinguish the hydrophilic and hydrophobic components of the 16-DS probe. The findings suggest that EPR spectroscopy is a valuable method for determining core fluidity in polymeric micelles.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 4","pages":"171 - 181"},"PeriodicalIF":2.2,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Design of inhibitor peptide sequences based on the interfacial knowledge of the protein G-IgG crystallographic complex and their binding studies with IgG 根据蛋白质 G-IgG 晶体复合物的界面知识设计抑制剂肽序列，并与 IgG 进行结合研究。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-03-17 DOI: 10.1007/s00249-024-01704-0

Neetu Tanwar, Rupal Ojha, Soumya Aggarwal, Vijay Kumar Prajapati, Manoj Munde

{"title":"Design of inhibitor peptide sequences based on the interfacial knowledge of the protein G-IgG crystallographic complex and their binding studies with IgG","authors":"Neetu Tanwar, Rupal Ojha, Soumya Aggarwal, Vijay Kumar Prajapati, Manoj Munde","doi":"10.1007/s00249-024-01704-0","DOIUrl":"10.1007/s00249-024-01704-0","url":null,"abstract":"<div><p>Protein–protein interactions (PPI) have emerged as valuable targets in medicinal chemistry due to their key roles in important biological processes. The modulation of PPI by small peptides offers an excellent opportunity to develop drugs against human diseases. Here, we exploited the knowledge of the binding interface of the IgG-protein G complex (PDB:1FCC) for designing peptides that can inhibit these complexes. Herein, we have designed several closely related peptides, and the comparison of results from experiments and computational studies indicated that all the peptides bind close to the expected binding site on IgG and the complexes are stable. A minimal sequence consisting of 11 amino acids (P5) with binding constants in the range of 100 nM was identified. We propose that the main affinity differences across the series of peptides arose from the presence of polar amino acid residues. Further, the molecular dynamic studies helped to understand the dynamic properties of complexes in terms of flexibility of residues and structural stability at the interface. The ability of P5 to compete with the protein G in recognizing IgG can help in the detection and purification of antibodies. Further, it can serve as a versatile tool for a better understanding of protein–protein interactions.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 3","pages":"159 - 170"},"PeriodicalIF":2.2,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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