Biophysical chemistry最新文献

{"title":"The structure, self-assembly and dynamics of lipid nanodiscs revealed by computational approaches","authors":"Beibei Wang ,&nbsp;D. Peter Tieleman","doi":"10.1016/j.bpc.2024.107231","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107231","url":null,"abstract":"<div><p>Nanodisc technology is increasingly being used in structural, biochemical and biophysical studies of membrane proteins. The computational approaches have revealed many important features of nanodisc assembly, structures and dynamics. Therefore, we reviewed the application of computational approaches, especially molecular modeling and molecular dyncamics (MD) simulations, to characterize nanodiscs, including the structural models, assembly and disassembly, protocols for modeling, structural properties and dynamics, and protein-lipid interactions in nanodiscs. More amazing computational studies about nanodiscs are looked forward to in the future.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"309 ","pages":"Article 107231"},"PeriodicalIF":3.8,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140342247","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}

{"title":"Dissecting the effect of ALS mutation S375G on the conformational properties and aggregation dynamics of TDP-43370-375 fragment","authors":"Zhengdong Xu ,&nbsp;Jianxin Zhang ,&nbsp;Jiaxing Tang ,&nbsp;Yehong Gong ,&nbsp;Yu Zou ,&nbsp;Qingwen Zhang","doi":"10.1016/j.bpc.2024.107230","DOIUrl":"10.1016/j.bpc.2024.107230","url":null,"abstract":"<div><p>The aggregation of transactive response deoxyribonucleic acid (DNA) binding protein of 43 kDa (TDP-43) into ubiquitin-positive inclusions is closely associated with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and chronic traumatic encephalopathy. The 370–375 fragment of TDP-43 (³⁷⁰GNNSYS³⁷⁵, TDP-43_370-375), the amyloidogenic hexapeptides, can be prone to forming pathogenic amyloid fibrils with the characteristic of steric zippers. Previous experiments reported the ALS-associated mutation, serine 375 substituted by glycine (S375G) is linked to early onset disease and protein aggregation of TDP-43. Based on this, it is necessary to explore the underlying molecular mechanisms. By utilizing all-atom molecular dynamics (MD) simulations of 102 μs in total, we investigated the impact of S375G mutation on the conformational ensembles and oligomerization dynamics of TDP-43_370-375 peptides. Our replica exchange MD simulations show that S375G mutation could promote the unstructured conformation formation and induce peptides to form a loose packed oligomer, thus inhibiting the aggregation of TDP-43_370-375. Further analyses suggest that S375G mutation displays a reduction effect on the number of total hydrogen bonds and contacts among TDP-43_370-375 peptides. Hydrogen bonding and polar interactions among TDP-43_370-375 peptides, as well as Y374-Y374 π-π stacking interaction, are attenuated by S375G mutation. Additional microsecond MD simulations demonstrate that S375G mutation could prohibit the conformational conversion to β-structure-rich aggregates and possess an inhibitory effect on the oligomerization dynamics of TDP-43_370-375. This study offers for the first time of molecular insights into the S375G mutation affecting the aggregation of TDP-43_370-375 at the atomic level, and may open new avenues in the development of future site-specific mutation therapeutics.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"310 ","pages":"Article 107230"},"PeriodicalIF":3.8,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403921","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}

{"title":"Probing pharmaceutically important amino acids L-isoleucine and L-tyrosine Solubilities: Unraveling the solvation thermodynamics in diverse mixed solvent systems","authors":"Jit Chakraborty ,&nbsp;Kalachand Mahali ,&nbsp;A.M.A. Henaish ,&nbsp;Jahangeer Ahmed ,&nbsp;Saad M. Alshehri ,&nbsp;Sanjay Roy","doi":"10.1016/j.bpc.2024.107229","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107229","url":null,"abstract":"<div><p>The study specifically investigates the solubilities of L-isoleucine and L-tyrosine in water-mixed solvent systems (DMF, DMSO, and ACN), exploring the behaviour of amino acids in complex environments. The experimental methods prioritize meticulous solvent purification to ensure reliable results. The work explores solubility data, uncovering temperature-dependent trends and intricate interactions influencing solubility in the chosen mixed solvent systems. The study emphasizes the impact of thermodynamic properties, solvent-solvent interactions, and amino acid structure on solubility patterns. The broader implications highlight the relevance of understanding amino acid behaviour in diverse solvent environments, offering potential applications in cosmetics and pharmaceutical industries. The distinct solubility patterns contribute valuable insights, enhancing on the understanding of the solution stability and interactions of L-isoleucine and L-tyrosine in different solvent systems. In conclusion, work suggests the enhanced utilization of L-isoleucine and L-tyrosine in various industries, driven by a profound understanding of their solubility in mixed solvent systems. The research expands our knowledge of amino acid behaviour, paving the way for advancements in industries relying on protein-based products and technologies.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"309 ","pages":"Article 107229"},"PeriodicalIF":3.8,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140328307","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}

{"title":"Metallo-β-lactamase inhibitors: A continuing challenge for combating antibiotic resistance","authors":"Su-Jin Kang ,&nbsp;Do-Hee Kim ,&nbsp;Bong-Jin Lee","doi":"10.1016/j.bpc.2024.107228","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107228","url":null,"abstract":"<div><p>β-lactam antibiotics are the most successful and commonly used antibacterial agents, but the emergence of resistance to these drugs has become a global health threat. The expression of β-lactamase enzymes produced by pathogens, which hydrolyze the amide bond of the β-lactam ring, is the major mechanism for bacterial resistance to β-lactams. In particular, among class A, B, C and D β-lactamases, metallo-β-lactamases (MBLs, class B β-lactamases) are considered crucial contributors to resistance in gram-negative bacteria. To combat β-lactamase-mediated resistance, great efforts have been made to develop β-lactamase inhibitors that restore the activity of β-lactams. Some β-lactamase inhibitors, such as diazabicyclooctanes (DBOs) and boronic acid derivatives, have also been approved by the FDA. Inhibitors used in the clinic can inactivate mostly serine-β-lactamases (SBLs, class A, C, and D β-lactamases) but have not been effective against MBLs until now. In order to develop new inhibitors particularly for MBLs, various attempts have been suggested. Based on structural and mechanical studies of MBL enzymes, several MBL inhibitor candidates, including taniborbactam in phase 3 and xeruborbactam in phase 1, have been introduced in recent years. However, designing potent inhibitors that are effective against all subclasses of MBLs is still extremely challenging. This review summarizes not only the types of β-lactamase and mechanisms by which β-lactam antibiotics are inactivated, but also the research finding on β-lactamase inhibitors targeting these enzymes. These detailed information on β-lactamases and their inhibitors could give valuable information for novel β-lactamase inhibitors design.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"309 ","pages":"Article 107228"},"PeriodicalIF":3.8,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320858","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}

{"title":"Improving synthesis and binding affinities of nucleic acid aptamers and their therapeutics and diagnostic applications","authors":"Malaya Mili ,&nbsp;Vinay Bachu ,&nbsp;Pooja Rani Kuri ,&nbsp;Naveen Kumar Singh ,&nbsp;Pranab Goswami","doi":"10.1016/j.bpc.2024.107218","DOIUrl":"10.1016/j.bpc.2024.107218","url":null,"abstract":"<div><p>Nucleic acid aptamers have captivated the attention of analytical and medicinal scientists globally due to their several advantages as recognition molecules over conventional antibodies because of their small size, simple and inexpensive synthesis, broad target range, and high stability in varied environmental conditions. These recognition molecules can be chemically modified to make them resistant to nuclease action in blood serum, reduce rapid renel clearance, improve the target affinity and selectivity, and make them amenable to chemically conjugate with a support system that facilitates their selective applications. This review focuses on the development of efficient aptamer candidates and their application in clinical diagnosis and therapeutic applications. Significant advances have been made in aptamer-based diagnosis of infectious and non-infectious diseases. Collaterally, the progress made in therapeutic applications of aptamers is encouraging, as evident from their use in diagnosing cancer, neurodegenerative diseases, microbial infection, and in imaging. This review also updates the progress on clinical trials of many aptamer-based products of commercial interests. The key development and critical issues on the subject have been summarized in the concluding remarks.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"309 ","pages":"Article 107218"},"PeriodicalIF":3.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271378","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}

{"title":"H2 production under stress: [FeFe]‑hydrogenases reveal strong stability in high pressure environments","authors":"Kristina Edenharter ,&nbsp;Michel W. Jaworek ,&nbsp;Vera Engelbrecht ,&nbsp;Roland Winter ,&nbsp;Thomas Happe","doi":"10.1016/j.bpc.2024.107217","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107217","url":null,"abstract":"<div><p>Hydrogenases are a diverse group of metalloenzymes that catalyze the conversion of H₂ into protons and electrons and the reverse reaction. A subgroup is formed by the [FeFe]‑hydrogenases, which are the most efficient enzymes of microbes for catalytic H₂ conversion. We have determined the stability and activity of two [FeFe]‑hydrogenases under high temperature and pressure conditions employing FTIR spectroscopy and the high-pressure stopped-flow methodology in combination with fast UV/Vis detection. Our data show high temperature stability and an increase in activity up to the unfolding temperatures of the enzymes. Remarkably, both enzymes reveal a very high pressure stability of their structure, even up to pressures of several kbars. Their high pressure-stability enables high enzymatic activity up to 2 kbar, which largely exceeds the pressure limit encountered by organisms in the deep sea and sub-seafloor on Earth.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107217"},"PeriodicalIF":3.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301462224000462/pdfft?md5=63a9b00b8624f7892908de829beda053&pid=1-s2.0-S0301462224000462-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134449","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}

{"title":"Understanding the bio-crystallization: An insight to therapeutic relevance","authors":"Vivek Pandey ,&nbsp;Tejasvi Pandey","doi":"10.1016/j.bpc.2024.107216","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107216","url":null,"abstract":"<div><p>In the realm of biomedical engineering and materials science, the synthesis of biomaterials plays a pivotal role in advancing therapeutic strategies for regeneration of tissues. The deliberate control of crystallization processes in biomaterial synthesis has emerged as a key avenue for tailoring the properties of these materials, enabling the design of innovative solutions for a wide array of medical applications. This review delves into the interplay between controlled crystallization and biomaterial synthesis, exploring its multifaceted applications in the therapeutic domains. The investigation encompasses a wide spectrum of matrices, ranging from small molecules to large biomolecules, highlighting their unique contributions in modulating crystallization processes. Furthermore, the review critically assesses the analytical techniques and methodologies employed to probe and characterize the depths of crystallization dynamics. Advanced imaging, spectroscopic, and computational tools are discussed in the context of unraveling the intricate mechanisms governing nucleation and crystallization processes within the organic matrix. Finally we delve in the applications of such advance material in therapeutics of hard and soft tissues.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107216"},"PeriodicalIF":3.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103759","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}

{"title":"Biophysical insight into anti-amyloidogenic nature of novel ionic Co(II)(phen)(H2O)4]+[glycinate]– chemotherapeutic drug candidate against human lysozyme aggregation.","authors":"Aiman Masroor ,&nbsp;Nida Zaidi ,&nbsp;Faisal Nabi ,&nbsp;Sadia Malik ,&nbsp;Siffeen Zehra ,&nbsp;Farukh Arjmand ,&nbsp;Nida Naseem ,&nbsp;Rizwan Hasan Khan","doi":"10.1016/j.bpc.2024.107214","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107214","url":null,"abstract":"<div><p>In the recent past, there has been an ever-increasing interest in the search for metal-based therapeutic drug candidates for protein misfolding disorders (PMDs) particularly neurodegenerative disorders such as Alzheimer's, Parkinson's, Prion's diseases, and amyotrophic lateral sclerosis. Also, different amyloidogenic variants of human lysozyme (HL) are involved in hereditary systemic amyloidosis. Metallo-therapeutic agents are extensively studied as antitumor agents, however, they are relatively unexplored for the treatment of non-neuropathic amyloidoses. In this work, inhibition potential of a novel ionic cobalt(II) therapeutic agent (CoTA) of the formulation [Co(phen)(H₂O)₄]⁺[glycinate]⁻ is evaluated against HL fibrillation. Various biophysical techniques viz., dye-binding assays, dynamic light scattering (DLS), differential scanning calorimetry (DSC), electron microscopy, and molecular docking experiments validate the proposed mechanism of inhibition of HL fibrillation by CoTA. The experimental corroborative results of these studies reveal that CoTA can suppress and slow down HL fibrillation at physiological temperature and pH. DLS and 1-anilino-8-naphthalenesulfonate (ANS) assay show that reduced fibrillation in the presence of CoTA is marked by a significant decrease in the size and hydrophobicity of the aggregates. Fluorescence quenching and molecular docking results demonstrate that CoTA binds moderately to the aggregation-prone region of HL (K_b = 6.6 × 10⁴ M⁻¹), thereby, inhibiting HL fibrillation. In addition, far-UV CD and DSC show that binding of CoTA to HL does not cause any change in the stability of HL. More importantly, CoTA attenuates membrane damaging effects of HL aggregates against RBCs. This study identifies inorganic metal complexes as a therapeutic intervention for systemic amyloidosis.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107214"},"PeriodicalIF":3.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999183","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}

{"title":"Targeting phenylalanine assemblies as a prospective disease-modifying therapy for phenylketonuria","authors":"Shira Shaham-Niv ,&nbsp;Assaf Ezra ,&nbsp;Dor Zaguri ,&nbsp;Stav Roni Shotan ,&nbsp;Elvira Haimov ,&nbsp;Hamutal Engel ,&nbsp;Tamara Brider ,&nbsp;Luba Simhaev ,&nbsp;Haim Michael Barr ,&nbsp;Lihi Adler-Abramovich ,&nbsp;Ehud Gazit","doi":"10.1016/j.bpc.2024.107215","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107215","url":null,"abstract":"<div><p>Phenylketonuria is characterized by the accumulation of phenylalanine, resulting in severe cognitive and neurological disorders if not treated by a remarkably strict diet. There are two approved drugs today, yet both provide only a partial solution. We have previously demonstrated the formation of amyloid-like toxic assemblies by aggregation of phenylalanine, suggesting a new therapeutic target to be further pursued. Moreover, we showed that compounds that halt the formation of these assemblies also prevent their resulting toxicity. Here, we performed high-throughput screening, searching for compounds with inhibitory effects on phenylalanine aggregation. Morin hydrate, one of the most promising hits revealed during the screen, was chosen to be tested in vivo using a phenylketonuria mouse model. Morin hydrate significantly improved cognitive and motor function with a reduction in the number of phenylalanine brain deposits. Moreover, while phenylalanine levels remained high, we observed a recovery in dopaminergic, adrenergic, and neuronal markers. To conclude, the ability of Morin hydrate to halt phenylalanine aggregation without reducing phenylalanine levels implies the toxic role of the phenylalanine assemblies in phenylketonuria and opens new avenues for disease-modifying treatment.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107215"},"PeriodicalIF":3.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014268","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}

{"title":"Molecular insights into nanoplastics-peptides binding and their interactions with the lipid membrane","authors":"Arianna Vismara,&nbsp;Alfonso Gautieri","doi":"10.1016/j.bpc.2024.107213","DOIUrl":"https://doi.org/10.1016/j.bpc.2024.107213","url":null,"abstract":"<div><p>Micro- and nanoplastics have become a significant concern, due to their ubiquitous presence in the environment. These particles can be internalized by the human body through ingestion, inhalation, or dermal contact, and then they can interact with environmental or biological molecules, such as proteins, resulting in the formation of the protein corona. However, information on the role of protein corona in the human body is still missing. Coarse-grain models of the nanoplastics and pentapeptides were created and simulated at the microscale to study the role of protein corona. Additionally, a lipid bilayer coarse-grain model was reproduced to investigate the behavior of the coronated nanoplastics in proximity of a lipid bilayer. Hydrophobic and aromatic amino acids have a high tendency to create stable bonds with all nanoplastics. Moreover, polystyrene and polypropylene establish bonds with polar and charged amino acids. When the coronated nanoplastics are close to a lipid bilayer, different behaviors can be observed. Polyethylene creates a single polymeric chain, while polypropylene tends to break down into its single chains. Polystyrene can both separate into its individual chains and remain aggregated. The protein corona plays an important role when interacting with the nanoplastics and the lipid membrane. More studies are needed to validate the results and to enhance the complexity of the systems.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"308 ","pages":"Article 107213"},"PeriodicalIF":3.8,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301462224000425/pdfft?md5=56ba4531afec9f8f82cd5b55d8b8820a&pid=1-s2.0-S0301462224000425-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992795","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}