Biophysica最新文献_第5页

Decomposition of Small Molecules for Fragment-Based Drug Design 基于片段的药物设计中的小分子分解

Biophysica Pub Date : 2023-05-24 DOI: 10.3390/biophysica3020024

Nikita N. Ivanov, D. Shulga, V. Palyulin

引用次数: 0

Phenotypic and Biomechanical Characteristics of Human Fetal Neural Progenitor Cells Exposed to Pesticide Compounds 人类胚胎神经祖细胞暴露于农药的表型和生物力学特征

Biophysica Pub Date : 2023-05-18 DOI: 10.3390/biophysica3020023

Marissa C. Sarsfield, Jennifer Vasu, Sabreen M. Abuoun, N. Allena, C. Kothapalli

{"title":"Phenotypic and Biomechanical Characteristics of Human Fetal Neural Progenitor Cells Exposed to Pesticide Compounds","authors":"Marissa C. Sarsfield, Jennifer Vasu, Sabreen M. Abuoun, N. Allena, C. Kothapalli","doi":"10.3390/biophysica3020023","DOIUrl":"https://doi.org/10.3390/biophysica3020023","url":null,"abstract":"Various forms of pesticides have been reported to be among the environmental toxicants, which are detrimental to human health. The active ingredients of these formulations can enter the human body through air, food, or water. Epidemiological studies suggest that these compounds strongly affect the developing brain in fetal and infant stages due to their ability to breach the underdeveloped blood–brain barrier. Since neural progenitor stem cells (NPCs) in the developing brain are the most vulnerable to these compounds, the mechanisms by which NPCs experience toxicity upon exposure to these chemicals must be investigated. Here, we assessed the viability of human fetal NPCs in 2D cultures in the presence of the active ingredients of six widely used pesticides using Live/Dead® and Hoechst staining. The IC50 values ranged from 4.1–201 μM. A significant drop in cell viability with increasing toxicant concentration (p < 0.01) was noted, with the order of toxicity being malathion < 4-aminopyridine < methoprene < prallethrin < temephos < pyriproxyfen. Changes in cellular biomechanical characteristics (Young’s modulus, tether force, membrane tension, and tether radius) were quantified using atomic force microscopy, whereas cell migration was elucidated over 48 h using a customized wound-healing assay. The Young’s modulus of fetal NPCs exposed to IC50/2 doses of these compounds was reduced by 38–70% and that of those exposed to IC50 doses was reduced by 71–80% (p < 0.001 vs. controls for both; p < 0.01 for IC50 vs. IC50/2 for each compound). Similar patterns were noted for tether forces and membrane tension in fetal NPCs. NPC migration was found to be compound type- and dose-dependent. These results attest to the significant detrimental effects of these compounds on various aspects of the human fetal NPC phenotype, and the utility of cell mechanics as a marker to assess developmental neurotoxicity.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41473059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developmental Pattern Formation: Spanish Contributions from a Biophysical Perspective 发展模式的形成：从生物物理角度看西班牙的贡献

Biophysica Pub Date : 2023-05-06 DOI: 10.3390/biophysica3020022

J. Buceta, Léna Guitou

引用次数: 0

Insights into Chemical Interactions and Related Toxicities of Deep Eutectic Solvents with Mammalian Cells Observed Using Synchrotron Macro–ATR–FTIR Microspectroscopy 利用同步加速器宏观atr - ftir显微光谱技术观察深共晶溶剂与哺乳动物细胞的化学相互作用和相关毒性

Biophysica Pub Date : 2023-05-04 DOI: 10.3390/biophysica3020021

Chandrasekhar B. Kothapalli, R. Mancera, P. Whitford, Saffron J. Bryant, Z. L. Shaw, Louisa Z. Y. Huang, A. Elbourne, A. Abraham, J. Vongsvivut, S. Holt, T. Greaves, G. Bryant

{"title":"Insights into Chemical Interactions and Related Toxicities of Deep Eutectic Solvents with Mammalian Cells Observed Using Synchrotron Macro–ATR–FTIR Microspectroscopy","authors":"Chandrasekhar B. Kothapalli, R. Mancera, P. Whitford, Saffron J. Bryant, Z. L. Shaw, Louisa Z. Y. Huang, A. Elbourne, A. Abraham, J. Vongsvivut, S. Holt, T. Greaves, G. Bryant","doi":"10.3390/biophysica3020021","DOIUrl":"https://doi.org/10.3390/biophysica3020021","url":null,"abstract":"Deep eutectic solvents (DESs) and ionic liquids (ILs) are highly tailorable solvents that have shown a lot of promise for a variety of applications including cryopreservation, drug delivery, and protein stabilisation. However, to date, there is very limited information on the detailed interactions of these solvents with mammalian cells. In this work, we studied six DESs and one IL that show promise as cryoprotective agents, applying synchrotron macro–ATR–FTIR to examine their effects on key biochemical components of HaCat mammalian cells. These data were paired with resazurin metabolic assays and neutron reflectivity experiments to correlate cellular interactions with cellular toxicity. Stark differences were observed even between solvents that shared similar components. In particular, it was found that solvents that are effective cryoprotective agents consistently showed interactions with cellular membranes, while high toxicity correlated with strong interactions of the DES/IL with nucleic acids and proteins. This work sheds new light on the interactions between novel solvents and cells that may underpin future biomedical applications.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43368922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Comparative Investigation of XPS Spectra of Oxidated Carbon Nanotubes and Graphene 氧化碳纳米管和石墨烯的XPS光谱比较研究

Biophysica Pub Date : 2023-04-13 DOI: 10.3390/biophysica3020020

V. Afanas’ev, G. S. Bocharov, A. Eletskii, Lidiya G. Lobanova, K. Maslakov, S. Savilov

引用次数: 3

Discovery of the Universal tRNA Binding Mode for the TsaD-like Components of the t6A tRNA Modification Pathway t6A tRNA修饰途径中tsad样组分的通用tRNA结合模式的发现

Biophysica Pub Date : 2023-04-12 DOI: 10.3390/biophysica3020019

B. Stec

{"title":"Discovery of the Universal tRNA Binding Mode for the TsaD-like Components of the t6A tRNA Modification Pathway","authors":"B. Stec","doi":"10.3390/biophysica3020019","DOIUrl":"https://doi.org/10.3390/biophysica3020019","url":null,"abstract":"Covalent addition of the threonylcarbamoyl group to N(6) of adenosine 37 (t6A modification) within the anticodon loop of several tRNAs is central to the translational fidelity in all known organisms. Structures for each of the enzyme components in the Tsa (t6A) pathway from all three kingdoms of life have been determined previously. In order to shed light on the poorly defined final step of t6A tRNA modification by TsaD-like components, we performed modeling studies. By docking a tRNA substrate molecule onto reanalyzed complete models of three TsaD-like proteins—TsaD from T. maritima, Qri7 from bacteria, and Kae1 from yeast—we identified a binding site that is common to all of them. An apparently universal binding mode has perfectly oriented tRNA for catalysis by TsaD. Furthermore, it suggests how the conformational changes in TsaD, in response to the binding of the additional regulatory subunits, control enzymatic activity. Re-refinement of the X-ray structure of the TsaBDE complex from T. maritima tentatively suggests that the moiety bound at the active site of the TsaD component is threonylcarbamoyl-AMP (TC-AMP). These findings suggest a detailed model for the mechanism of the catalytic reaction carried out by the TsaD-like components that explains the transfer of unstable TC-AMP from TsaC to TsaD proteins in the t6A modification pathway.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48445588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silica In Silico: A Molecular Dynamics Characterization of the Early Stages of Protein Embedding for Atom Probe Tomography 硅中的二氧化硅:原子探针断层扫描蛋白质包埋早期阶段的分子动力学表征

Biophysica Pub Date : 2023-04-11 DOI: 10.3390/biophysica3020018

Giovanni Novi Inverardi, Francesco Carnovale, Lorenzo Petrolli, S. Taioli, G. Lattanzi

{"title":"Silica In Silico: A Molecular Dynamics Characterization of the Early Stages of Protein Embedding for Atom Probe Tomography","authors":"Giovanni Novi Inverardi, Francesco Carnovale, Lorenzo Petrolli, S. Taioli, G. Lattanzi","doi":"10.3390/biophysica3020018","DOIUrl":"https://doi.org/10.3390/biophysica3020018","url":null,"abstract":"A novel procedure for the application of atom probe tomography (APT) to the structural analysis of biological systems, has been recently proposed, whereby the specimen is embedded by a silica matrix and ablated by a pulsed laser source. Such a technique, requires that the silica primer be properly inert and bio-compatible, keeping the native structural features of the system at hand, while condensing into an amorphous, glass-like coating. In this work, we propose a molecular dynamics protocol, aimed at depicting and characterizing the earliest stages of the embedding process of small biomolecules in a solution of water and orthosilicic acid, here, taken as a precursor of the silica matrix. Overall, we observe a negligible influence of orthosilicic acid on the behavior of stable folded systems (such as ubiquitin). Conversely, intrinsically disordered and unstable peptides are affected by the coating, the latter seemingly inhibiting the fluctuations of flexible moieties. While further scrutiny is in order, our assessment offers a first mechanistic insight of the effects of orthosilicic acid, thereby validating its use in the proposed innovative application of APT to the structural resolution of protein molecules.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46818610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coarse-Grained MD Simulations of Opioid Interactions with the μ-Opioid Receptor and the Surrounding Lipid Membrane 阿片与μ-阿片受体及周围脂质膜相互作用的粗粒度MD模拟

Biophysica Pub Date : 2023-04-06 DOI: 10.3390/biophysica3020017

Sourav Ray, K. Fackeldey, C. Stein, M. Weber

{"title":"Coarse-Grained MD Simulations of Opioid Interactions with the μ-Opioid Receptor and the Surrounding Lipid Membrane","authors":"Sourav Ray, K. Fackeldey, C. Stein, M. Weber","doi":"10.3390/biophysica3020017","DOIUrl":"https://doi.org/10.3390/biophysica3020017","url":null,"abstract":"In our previous studies, a new opioid (NFEPP) was developed to only selectively bind to the μ-opoid receptor (MOR) in inflamed tissue and thus avoid the severe side effects of fentanyl. We know that NFEPP has a reduced binding affinity to MOR in healthy tissue. Inspired by the modelling and simulations performed by Sutcliffe et al., we present our own results of coarse-grained molecular dynamics simulations of fentanyl and NFEPP with regards to their interaction with the μ-opioid receptor embedded within the lipid cell membrane. For technical reasons, we have slightly modified Sutcliffe’s parametrisation of opioids. The pH-dependent opioid simulations are of interest because while fentanyl is protonated at the physiological pH, NFEPP is deprotonated due to its lower pKa value than that of fentanyl. Here, we analyse for the first time whether pH changes have an effect on the dynamical behaviour of NFEPP when it is inside the cell membrane. Besides these changes, our analysis shows a possible alternative interaction of NFEPP at pH 7.4 outside the binding region of the MOR. The interaction potential of NFEPP with MOR is also depicted by analysing the provided statistical molecular dynamics simulations with the aid of an eigenvector analysis of a transition rate matrix. In our modelling, we see differences in the XY-diffusion profiles of NFEPP compared with fentanyl in the cell membrane.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48367001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational Modeling of the Interaction of Molecular Oxygen with the miniSOG Protein—A Light Induced Source of Singlet Oxygen 分子氧与miniSOG蛋白- a单线态氧光诱导源相互作用的计算模型

Biophysica Pub Date : 2023-04-02 DOI: 10.3390/biophysica3020016

Igor V. Polyakov, A. Kulakova, A. Nemukhin

引用次数: 0

Comparison of Empirical Zn2+ Models in Protein–DNA Complexes 蛋白质- dna复合物的经验Zn2+模型比较

Biophysica Pub Date : 2023-03-20 DOI: 10.3390/biophysica3010014

S. Volkenandt, P. Imhof

{"title":"Comparison of Empirical Zn2+ Models in Protein–DNA Complexes","authors":"S. Volkenandt, P. Imhof","doi":"10.3390/biophysica3010014","DOIUrl":"https://doi.org/10.3390/biophysica3010014","url":null,"abstract":"Zinc ions are the second most abundant ions found in humans. Their role in proteins can be merely structural but also catalytic, owing to their transition metal character. Modelling their geometric–coordination versatility by empirical force fields is, thus, a challenging task. In this work, we evaluated three popular models, specifically designed to represent zinc ions with regard to their capability of preserving structural integrity. To this end, we performed molecular dynamics simulations of two zinc-containing protein–DNA complexes, which differed in their zinc coordination, i.e., four cysteines or two cysteines and two histidines. The most flexible non-bonded 12-6-4 Lennard–Jones-type model shows a preference for six-fold coordination of the Zn2+-ions in contradiction to the crystal structure. The cationic dummy atom model favours tetrahedral geometry, whereas the bonded extended zinc AMBER force field model, by construction, best preserves the initial geometry of a regular or slightly distorted tetrahedron. Our data renders the extended zinc AMBER force field the best model for structural zinc ions in a given geometry. In more complicated cases, though, more flexible models may be advantageous.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42714852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0