Biophysics and physicobiology最新文献

{"title":"Exploring hydrophilic sequence space to search for uncharted foldable proteins by AlphaFold2.","authors":"Naoki Tomita, Hiroki Onoda, Leonard M G Chavas, George Chikenji","doi":"10.2142/biophysico.bppb-v22.0005","DOIUrl":"10.2142/biophysico.bppb-v22.0005","url":null,"abstract":"<p><p>Proteins typically fold into unique three-dimensional structures largely driven by interactions between hydrophobic amino acids. This understanding has helped improve our knowledge of protein folding. However, recent research has shown an exception to this idea, demonstrating that specific threonine-rich peptides have a strong tendency to form β-hairpin structures, even in the highly hydrophilic amino acid sequences. This finding suggests that the hydrophilic amino acid sequence space still leaves room for exploring foldable amino acid sequences. In this study, we conducted a systematic exploration of the repetitive amino acid sequence space by AlphaFold2 (AF2), with a focus on sequences composed exclusively of hydrophilic residues, to investigate their potential for adopting unique structures. As a result, the sequence space exploration suggested that several repetitive threonine-rich sequences adopt distinctive conformations and these conformational shapes can be influenced by the length of the sequence unit. Moreover, the analysis of structural dataset suggested that threonine contributes to the structural stabilization by forming non-polar atom packing that tolerates unsatisfied hydrogen bonds, and while also supporting other residues in forming hydrogen bonds. Our findings will broaden the horizons for the discovery of foldable amino acid sequences consisting solely of hydrophilic residues and help us clarify the unknown mechanisms of protein structural stabilization.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"22 1","pages":"e220005"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement in positional accuracy of neural-network predicted hydration sites of proteins by incorporating atomic details of water-protein interactions and site-searching algorithm.","authors":"Kochi Sato, Masayoshi Nakasako","doi":"10.2142/biophysico.bppb-v22.0004","DOIUrl":"10.2142/biophysico.bppb-v22.0004","url":null,"abstract":"<p><p>Visualization of hydration structures over the entire protein surface is necessary to understand why the aqueous environment is essential for protein folding and functions. However, it is still difficult for experiments. Recently, we developed a convolutional neural network (CNN) to predict the probability distribution of hydration water molecules over protein surfaces and in protein cavities. The deep network was optimized using solely the distribution patterns of protein atoms surrounding each hydration water molecule in high-resolution X-ray crystal structures and successfully provided probability distributions of hydration water molecules. Despite the effectiveness of the probability distribution, the positional differences of the predicted positions obtained from the local maxima as predicted sites remained inadequate in reproducing the hydration sites in the crystal structure models. In this work, we modified the deep network by subdividing atomic classes based on the electronic properties of atoms composing amino acids. In addition, the exclusion volumes of each protein atom and hydration water molecule were taken to predict the hydration sites from the probability distribution. These information on chemical properties of atoms leads to an improvement in positional prediction accuracy. We selected the best CNN from 47 CNNs constructed by systematically varying the number of channels and layers of neural networks. Here, we report the improvements in prediction accuracy by the reorganized CNN together with the details in the architecture, training data, and peak search algorithm.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"22 1","pages":"e220004"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Product release and substrate entry of aldehyde deformylating oxygenase revealed by molecular dynamics simulations.","authors":"Masataka Yoshimura, Munehito Arai","doi":"10.2142/biophysico.bppb-v22.0003","DOIUrl":"10.2142/biophysico.bppb-v22.0003","url":null,"abstract":"<p><p>Cyanobacteria can produce alkanes equivalent to diesel fuels through a two-step enzymatic process involving acyl-(acyl carrier protein) reductase (AAR) and aldehyde deformylating oxygenase (ADO), providing a potential renewable biofuel source. AAR binds to ADO for efficient delivery of an aldehyde substrate and they have been proposed to dissociate when the alkane product is released from the same site as the substrate entrance of ADO. However, the dynamics of the substrate and product in ADO during substrate entry and product release are poorly understood. Here, we performed molecular dynamics (MD) simulations of ADO in the presence of substrate or product. We found that while the aldehyde substrate remains close to the active center of ADO before catalysis, the alkane product can dynamically rotate within the hydrophobic tunnel inside ADO toward the product exit after catalysis. Furthermore, the parallel cascade selection (PaCS)-MD simulations of ADO and the AAR/ADO complex identified the locations of the substrate entrance and the multiple exits for product release on ADO. Strikingly, the PaCS-MD simulations revealed that the alkane product can be released from the exit different from the substrate entrance without dissociation of AAR. Based on these results, we propose a reaction model for efficient alkane production by the AAR/ADO complex in which aldehydes and alkanes are synthesized simultaneously while AAR and ADO remain bound, and the aldehyde substrate can be delivered to ADO immediately after alkane release. Our study will be useful in improving the efficiency of bioalkane production using AAR and ADO.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"22 1","pages":"e220003"},"PeriodicalIF":1.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of protoplasmic streaming over the entire body of <i>Physarum</i> plasmodium, and estimation of the transport and mixing of protoplasma through the intricate vein network.","authors":"Yo Sato, Charles Fosseprez, Yukinori Nishigami, Katsuhiko Sato, Hiroshi Orihara, Toshiyuki Nakagaki","doi":"10.2142/biophysico.bppb-v22.0002","DOIUrl":"10.2142/biophysico.bppb-v22.0002","url":null,"abstract":"<p><p>Transport networks spanning the entire body of an organism are key infrastructures for achieving a functional system and facilitating the distribution of nutrients and signals. The large amoeba-like organism <i>Physarum polycephalum</i> has gained attention as a useful model for studying biological transport networks owing to its visible and rapidly adapting vein structure. Using particle-tracking velocimetry, we measured the flow velocity of protoplasmic streaming over the entire body of <i>Physarum</i> plasmodia during the development of its intricate vein network. Based on these measurements, we estimated how the protoplasm is transported and mixed throughout the body. Our findings suggest that the vein network significantly enhances effective mixing of the protoplasm throughout the organism, which may have important physiological implications for nutrient distribution and signaling.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"22 1","pages":"e220002"},"PeriodicalIF":1.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-infrared spectroscopic study of blood flow changes in the dorsolateral prefrontal cortex during pain relief by odor stimulation.","authors":"Yuki Okamura, Shogo Takayama, Kengo Namiki, Fusako Koshikawa, Etsuro Ito","doi":"10.2142/biophysico.bppb-v22.0001","DOIUrl":"10.2142/biophysico.bppb-v22.0001","url":null,"abstract":"<p><p>Chronic pain is an unpleasant experience caused by sensory and emotional instability, sometimes independent of actual tissue damage. Pain relief can greatly impact psychologic, social, and economic well-being. Aromatherapy has long been used to alleviate pain and previous studies demonstrated that odors alter cerebral blood flow. In the present study, we used near-infrared spectroscopy to test our hypothesis that olfactory stimulation contributes to pain relief by altering cerebral blood flow in brain regions associated with pain. Pain was induced by transcutaneous electrical stimulation and assessed using a visual analog scale. Peppermint and lavender olfactory stimuli were used. Based on previous results, we focused on the prefrontal cortex. A placebo experiment in which only air stimulation was presented revealed minimal changes in blood flow in the ventromedial prefrontal cortex when comparing pain stimulation alone and a combination of placebo and pain stimulation. We then examined changes in blood flow following the presentation of peppermint or lavender scents. Significant differences in blood flow were observed in the dorsolateral prefrontal cortex (DLPFC) between pain stimulation alone and pain stimulation combined with odor stimulation. These findings supported our previous finding that the DLPFC is involved in pain relief by patch-adhered stimulation, but odor stimulation activated the right DLPFC whereas patch-adhered stimulation suppressed the left DLPFC. One interpretation of the discrepancy is that the contrast of activation between the right and left DLPFC is important in pain relief. Our research will help to elucidate the neurologic mechanisms underlying pain relief.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"22 1","pages":"e220001"},"PeriodicalIF":1.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuron with well-designed ionic system.","authors":"Takayoshi Tsubo","doi":"10.2142/biophysico.bppb-v21.0028","DOIUrl":"10.2142/biophysico.bppb-v21.0028","url":null,"abstract":"<p><p>Neurons have an ionic system with several types of ion pumps and ion channels on their membranes. Each ion pump creates a specific difference in ion concentration inside and outside the neuron, and the energy resulting from this difference in concentration is maintained inside the neuron as a resting potential. Each ion channel senses the necessary situation, opens the channel, and allows the corresponding ion to pass through to perform its corresponding role. This ionic system realizes important functions such as (i) fast conduction of action potentials, (ii) achieving synaptic integration in response to several inputs with a time lag, and (iii) the information processing functions by neural circuits. However, the mechanisms by which these functions are realized have remained unclear. Therefore, based on the reports on various highly polymeric ion pumps, ion channels, cell membranes, and other components that have been elucidated so far, author analyzed how this ionic system can realize the above important functions from an electrical circuit designer point of view. As a result of a series of analyses, it was found that neurons realize each function by making full use of high-density packaging technology based on basic electrical principles and making maximum use of the extremely high dielectric properties of the ionic fluid of neurons. In other words, neuron looks to equip well designed ionic system which is the collaboration by designers of proteins and membranes that perform advanced functions and designers of electrical circuits that utilize them to achieve important functions electrically.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 4","pages":"e210028"},"PeriodicalIF":1.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study of alpha-glucosidase inhibition of four Vietnamese medicinal plants <i>Combretum quadrangulare</i>, <i>Dicranopteris linearis</i>, <i>Psychotria adenophylla</i>, and <i>Garcinia schomburgkiana</i>: <i>In vitro</i> and <i>in vivo</i> studies.","authors":"Thi-Hong-Tuoi Do, Thuc-Huy Duong, Huu-Hung Nguyen, Thanh-Sang Vo, Ngoc-Hong Nguyen, Huong Thuy Le","doi":"10.2142/biophysico.bppb-v21.0027","DOIUrl":"10.2142/biophysico.bppb-v21.0027","url":null,"abstract":"<p><p>Four medicinal plants <i>C. quadrangulare</i>, <i>D. linearis</i>, <i>P. adenophylla</i>, and <i>G. schomburgkiana</i> growing in the South of Vietnam were investigated for their alpha-glucosidase inhibition. The crude methanol extract of <i>C. quadrangulare</i> was determined to be the most active extract, then was selected for further <i>in vivo</i> assays including antidiabetic study and toxicity. <i>In vitro</i> alpha-glucosidase inhibition of four medicinal plants <i>C. quadrangulare</i>, <i>D. linearis</i>, <i>P. adenophylla</i>, and <i>G. schomburgkiana</i> was screened using standard procedures. <i>In vivo</i> antidiabetic activity, acute toxicity and subchronical toxicity of <i>C. quadrangulare</i> leaves was assessed on Swiss albino mice. Swiss albino mice were induced with diabetes by intraperitoneal injection of alloxan at a dose of 150 mg/kg body weight. High-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) were used to detect the bioactive components of <i>C. quadrangulare</i> leaves. All crude extracts from the studied plants showed promising alpha-glucosidase inhibition, with IC₅₀ values ranging from 2.4 to 35.3 μg/mL. The methanol extract of <i>C. quadrangulare</i> leaves was determined to be the most active extract. This extract was then selected for antidiabetic assay using alloxan induced model of type 2 diabetes mellitus mice. The results indicated that the extract at a dose of 400 mg/kg can effectively decrease blood glucose levels that is comparable to that of glibenclamide 2 mg/kg. This compound showed moderate activity toward alpha-glucosidase. Therefore, our study indicated that <i>C. quadrangulare</i>, <i>D. linearis</i>, <i>P. adenophylla</i>, and <i>G. schomburgkiana</i> extract are potential materials for producing α-glucosidase inhibitor drugs.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 4","pages":"e210027"},"PeriodicalIF":1.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological analysis of hyperkalemic cardiomyocytes using a multielectrode array system.","authors":"Kentaro Kito, Masahito Hayashi, Tomoyuki Kaneko","doi":"10.2142/biophysico.bppb-v21.0026","DOIUrl":"10.2142/biophysico.bppb-v21.0026","url":null,"abstract":"<p><p>The action potential of cardiomyocytes is controlled by electrolytes in serum such as Na⁺, K⁺ and Ca²⁺. Hyperkalemia, which refers to an abnormally high concentration of K⁺ in the blood, can induce lethal arrythmia. In this study, the extracellular potentials on a sheet of chick embryonic cardiomyocytes were investigated at increasing K⁺ concentrations using a multielectrode array system. We observed that the interspike interval (ISI) was prolonged by approximately 3.5 times; dV/dt (the slope of a waveform) was decreased by more than five times; the field potential duration (FPD) was shortened by 20%, and the conduction velocity was about half at 12 mM K⁺ against the control (4 mM K⁺). In calcium therapy for hyperkalemia, although the prolongation of ISI under hyperkalemic conditions was restored, the slowing of conduction velocity, the decrease in dV/dt, and the shortening of FPD were not recovered by increasing the extracellular Ca²⁺ concentration. These findings provide a comprehensive understanding of cardiomyocytes in hyperkalemic conditions. Electrophysiological analysis by varying the extracellular concentrations of multiple types of electrolytes will be useful for the further discussion of the results of this study and for the interpretation of the waveforms obtained by measuring the extracellular potential.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 4","pages":"e210026"},"PeriodicalIF":1.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Announcement of BPPB paper awards 2024.","authors":"Haruki Nakamura","doi":"10.2142/biophysico.bppb-v21.0025","DOIUrl":"https://doi.org/10.2142/biophysico.bppb-v21.0025","url":null,"abstract":"","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 4","pages":"e210025"},"PeriodicalIF":1.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid in vitro method to assemble and transfer DNA fragments into the JCVI-syn3B minimal synthetic bacterial genome through Cre/<i>loxP</i> system.","authors":"Atsuko Uenoyama, Hana Kiyama, Mone Mimura, Makoto Miyata","doi":"10.2142/biophysico.bppb-v21.0024","DOIUrl":"10.2142/biophysico.bppb-v21.0024","url":null,"abstract":"<p><p>JCVI-syn3B (syn3B), a minimal synthetic bacterium that only possesses essential genes, facilitates the examination of heterogeneous gene functions in minimal life. Conventionally, <i>Escherichia coli</i> is used to construct DNA fragments for gene transfer into the syn3B genome through Cre/<i>loxP</i> system. However, the construction process is challenging and time-consuming due to various issues, including the inhibition of <i>E. coli</i> growth and unexpected recombination, especially with AT-rich DNA sequences such as those found in <i>Mycoplasma</i> genes. Therefore, in this study, we aimed to develop a new transformation method to overcome these issues. We assembled the vector and target DNA fragments using an in vitro homologous recombination system and subsequently transferred the products into the syn3B genome. We obtained approximately 10³~10⁴ recombinant colonies per milliliter of the original culture in eight days, which is four days shorter than the conventional period, without any recombination issues, even for AT-rich DNA. This method may be applicable to other gene manipulation systems based on Cre/<i>loxP</i> system.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 4","pages":"e210024"},"PeriodicalIF":1.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}