Biophysics and physicobiology最新文献

Data-driven score tuning for ChooseLD: A structure-based drug design algorithm with empirical scoring and evaluation of ligand-protein docking predictability. ChooseLD的数据驱动评分调整：一种基于结构的药物设计算法，具有配体-蛋白质对接可预测性的经验评分和评估。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-09-21 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0021

Akihiro Masuda, Daichi Sadato, Mitsuo Iwadate

{"title":"Data-driven score tuning for ChooseLD: A structure-based drug design algorithm with empirical scoring and evaluation of ligand-protein docking predictability.","authors":"Akihiro Masuda, Daichi Sadato, Mitsuo Iwadate","doi":"10.2142/biophysico.bppb-v21.0021","DOIUrl":"10.2142/biophysico.bppb-v21.0021","url":null,"abstract":"Computerized molecular docking methodologies are pivotal in in-silico screening, a crucial facet of modern drug design. ChooseLD, a docking simulation software, combines structure- and ligand-based drug design methods with empirical scoring. Despite advancements in computerized molecular docking methodologies, there remains a gap in optimizing the predictive capabilities of docking simulation software. Accordingly, using the docking scores output by ChooseLD, we evaluated its performance in predicting the bioactivity of G-protein coupled receptor (GPCR) and kinase bioactivity, specifically focusing on Ki and IC50 values. We evaluated the accuracy of our algorithm through a comparative analysis using force-field-based predictions from AutoDock Vina. Our findings suggested that the modified ChooseLD could accurately predict the bioactivity, especially in scenarios with a substantial number of known ligands. These findings highlight the importance of selecting algorithms based on the characteristics of the prediction targets. Furthermore, addressing partial model fitting with database knowledge was demonstrated to be effective in overcoming this challenge. Overall, these findings contribute to the refinement and optimization of methodologies in computer-aided drug design, ultimately advancing the efficiency and reliability of in-silico screening processes.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 3","pages":"e210021"},"PeriodicalIF":1.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974184","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}

引用次数: 0

Four-color single-molecule imaging system for tracking GPCR dynamics with fluorescent HiBiT peptide. 利用荧光HiBiT肽跟踪GPCR动力学的四色单分子成像系统。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-09-20 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0020

Toshiki Yoda, Yasushi Sako, Asuka Inoue, Masataka Yanagawa

{"title":"Four-color single-molecule imaging system for tracking GPCR dynamics with fluorescent HiBiT peptide.","authors":"Toshiki Yoda, Yasushi Sako, Asuka Inoue, Masataka Yanagawa","doi":"10.2142/biophysico.bppb-v21.0020","DOIUrl":"10.2142/biophysico.bppb-v21.0020","url":null,"abstract":"Single-molecule imaging provides information on diffusion dynamics, oligomerization, and protein-protein interactions in living cells. To simultaneously monitor different types of proteins at the single-molecule level, orthogonal fluorescent labeling methods with different photostable dyes are required. G-protein-coupled receptors (GPCRs), a major class of drug targets, are prototypical membrane receptors that have been studied using single-molecule imaging techniques. Here we developed a method for labeling cell-surface GPCRs inspired by the HiBiT system, which utilizes the high affinity complementation between LgBiT and HiBiT fragments of the NanoLuc luciferase. We synthesized four fluorescence-labeled HiBiT peptides (F-FiBiTs) with a different color dye (Setau-488, TMR, SaraFluor 650 and SaraFluor 720). We constructed a multicolor total internal reflection fluorescence microscopy system that allows us to track four color dyes simultaneously. As a proof-of-concept experiment, we labeled an N-terminally LgBiT-fused GPCR (Lg-GPCR) with a mixture of the four F-FiBiTs and successfully tracked each dye within a cell at the single-molecule level. The F-FiBiT-labeled Lg-GPCRs showed agonist-dependent changes in the diffusion dynamics and accumulation into the clathrin-coated pits as observed with a conventional method using a C-terminally HaloTag-fused GPCR. Taking advantage of luciferase complementation by the F-FiBiT and Lg-GPCRs, the F-FiBiT was also applicable to bioluminescence plate-reader-based assays. By combining existing labeling methods such as HaloTag, SNAP-tag, and fluorescent proteins, the F-FiBiT method will be useful for multicolor single-molecule imaging and will enhance our understanding of GPCR signaling at the single-molecule level.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 3","pages":"e210020"},"PeriodicalIF":1.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974224","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}

引用次数: 0

Monitoring of enzymatic cleavage reaction of GST-fusion protein on biolayer interferometry sensor. 利用生物层干涉仪传感器监测 GST 融合蛋白的酶裂解反应。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0019

Sena Tarumoto, Sei Inoue, Rina Yanagimoto, Takashi Saitoh

{"title":"Monitoring of enzymatic cleavage reaction of GST-fusion protein on biolayer interferometry sensor.","authors":"Sena Tarumoto, Sei Inoue, Rina Yanagimoto, Takashi Saitoh","doi":"10.2142/biophysico.bppb-v21.0019","DOIUrl":"10.2142/biophysico.bppb-v21.0019","url":null,"abstract":"Biolayer interferometry (BLI) is an optical sensor-based analytical method primarily used for analyzing interactions between biomolecules. In this study, we explored the application of BLI to observe the cleavage reaction of glutathione S-transferase (GST)-tagged fusion protein by human rhinovirus (HRV) 3C protease on a BLI sensor as a new application of the BLI method. The soluble domain of the Tic22 protein from Plasmodium falciparum was expressed and purified as a GST-tagged fusion protein, GST-Tic22, in Escherichia coli. A cleavage sequence for HRV 3C protease was inserted between the GST tag and the soluble domain of Tic22. First, we confirmed that GST-Tic22 was specifically cleaved at the inserted sequence by HRV 3C protease using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Following this, GST-Tic22 was immobilized on a BLI sensor, and enzymatic cleavage by the HRV 3C protease was monitored. We observed that the soluble domain of Tic22 was cleaved and released into the buffer over time, and this reaction was dependent on the enzyme concentration. This result demonstrates that the BLI method can be used to evaluate the cleavage of the GST tag by the HRV 3C protease in real time under different conditions. This method enables a more efficient search for the optimal conditions for the tag cleavage reaction in fusion proteins, a process that has historically required a substantial amount of time and effort.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 3","pages":"e210019"},"PeriodicalIF":1.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974260","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}

引用次数: 0

Function of nodal cilia in left-right determination: Mechanical regulation in initiation of symmetry breaking. 节点纤毛在左右决定中的功能：启动对称性破坏过程中的机械调节

IF 1.6

Biophysics and physicobiology Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0018

Takanobu A Katoh

{"title":"Function of nodal cilia in left-right determination: Mechanical regulation in initiation of symmetry breaking.","authors":"Takanobu A Katoh","doi":"10.2142/biophysico.bppb-v21.0018","DOIUrl":"10.2142/biophysico.bppb-v21.0018","url":null,"abstract":"Visceral organs in vertebrates are arranged with left-right asymmetry; for example, the heart is located on the left side of the body. Cilia at the node of mouse early embryos play an essential role in determining this left-right asymmetry. Using information from the anteroposterior axis, motile cilia at the central region of the node generate leftward nodal flow. Immotile cilia at the periphery of the node mechanically sense the direction of leftward nodal flow in a manner dependent on the polarized localization of Pkd2, which is localized on the dorsal side of cilia. Therefore, only left-side cilia are activated by leftward nodal flow. This activation results in frequent calcium transients in the cilia via the Pkd2 channel, which leads to the degradation of Dand5 mRNA only at the left-side crown-cells. This process is the mechanism of initial determination of the left-side-specific signal. In this review, we provide an overview of initial left-right symmetry breaking that occurs at the node, focusing mainly on a recent biophysical study that revealed the function of nodal immotile cilia using advanced microscopic techniques, such as optical tweezers and super-resolution microscopy.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 3","pages":"e210018"},"PeriodicalIF":1.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974232","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}

引用次数: 0

Chemical tongues as multipurpose bioanalytical tools for the characterization of complex biological samples. 化学舌作为多用途生物分析工具，用于表征复杂的生物样本。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0017

Shunsuke Tomita, Hiroka Sugai

{"title":"Chemical tongues as multipurpose bioanalytical tools for the characterization of complex biological samples.","authors":"Shunsuke Tomita, Hiroka Sugai","doi":"10.2142/biophysico.bppb-v21.0017","DOIUrl":"https://doi.org/10.2142/biophysico.bppb-v21.0017","url":null,"abstract":"Chemical tongues are emerging powerful bioanalytical tools that mimic the mechanism of the human taste system to recognize the comprehensive characteristics of complex biological samples. By using an array of chromogenic or fluorogenic probes that interact non-specifically with various components in the samples, this tool generates unique colorimetric or fluorescence patterns that reflect the biological composition of a sample. These patterns are then analyzed using multivariate analysis or machine learning to distinguish and classify the samples. This review focuses on our efforts to provide an overview of the fundamental principles of chemical tongues, probe design, and their applications as versatile tools for analyzing proteins, cells, and bacteria in biological samples. Compared to conventional methods that rely on specific targeting (e.g., antibodies or enzymes) or comprehensive omics analyses, chemical tongues offer advantages in terms of cost and the ability to analyze samples without the need for specific biomarkers. The complementary use of chemical tongues and conventional methods is expected to enable a more detailed understanding of biological samples and lead to the elucidation of new biological phenomena.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 3","pages":"e210017"},"PeriodicalIF":1.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485131","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}

引用次数: 0

Unraveling the fastest myosin: Discovery history and structure-function relationships of algae Chara myosin XI. 揭开最快肌球蛋白的神秘面纱：藻类查拉肌球蛋白 XI 的发现历史和结构功能关系。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-07-17 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0016

Kohji Ito, Takeshi Haraguchi

引用次数: 0

Internal structure of Mycoplasma mobile gliding machinery analyzed by negative staining electron tomography. 通过负染色电子断层扫描分析支原体移动滑行机械的内部结构。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-05-28 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0015

Minoru Fukushima, Takuma Toyonaga, Yuhei O Tahara, Daisuke Nakane, Makoto Miyata

{"title":"Internal structure of Mycoplasma mobile gliding machinery analyzed by negative staining electron tomography.","authors":"Minoru Fukushima, Takuma Toyonaga, Yuhei O Tahara, Daisuke Nakane, Makoto Miyata","doi":"10.2142/biophysico.bppb-v21.0015","DOIUrl":"https://doi.org/10.2142/biophysico.bppb-v21.0015","url":null,"abstract":"Mycoplasma mobile is a parasitic bacterium that forms gliding machinery on the cell pole and glides on a solid surface in the direction of the cell pole. The gliding machinery consists of both internal and surface structures. The internal structure is divided into a bell at the front and chain structure extending from the bell. In this study, the internal structures prepared under several conditions were analyzed using negative-staining electron microscopy and electron tomography. The chains were constructed by linked motors containing two complexes similar to ATP synthase. A cylindrical spacer with a maximum diameter of 6 nm and a height of 13 nm, and anonymous linkers with a diameter of 0.9-8.3 nm and length of 14.7±6.9 nm were found between motors. The bell is bowl-shaped and features a honeycomb surface with a periodicity of 8.4 nm. The chains of the motor are connected to the rim of the bell through a wedge-shaped structure. These structures may play roles in the assembly and cooperation of gliding machinery units.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 2","pages":"e210015"},"PeriodicalIF":1.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116818","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}

引用次数: 0

Application of single-molecule analysis to singularity phenomenon of cells. 将单分子分析应用于细胞的奇异现象。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-05-08 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.s018

Michio Hiroshima, Hiroko Bannai, Gen Matsumoto, Masahiro Ueda

{"title":"Application of single-molecule analysis to singularity phenomenon of cells.","authors":"Michio Hiroshima, Hiroko Bannai, Gen Matsumoto, Masahiro Ueda","doi":"10.2142/biophysico.bppb-v21.s018","DOIUrl":"10.2142/biophysico.bppb-v21.s018","url":null,"abstract":"Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics. The apparatus, called automated in-cell single-molecule imaging system (AiSIS), achieves a throughput that is a hundred-fold higher than conventional manual imaging operations, enabling the analysis of molecular events by individual cells across a large population. Here, using AiSIS, we demonstrate the single-molecule imaging of molecular behaviors and reactions related to tau protein aggregation, which is considered a singularity phenomenon in neurological disorders. Changes in the dynamics and kinetics of molecular events were observed inside and on the basal membrane of cells after the induction of aggregation. Additionally, to detect rare cells based on the molecular behavior, we developed a method to identify the state of individual cells defined by the quantitative distribution of molecular mobility and clustering. Using this method, cellular variations in receptor behavior were shown to decrease following ligand stimulation. This cell state analysis based on large-scale single-molecule imaging by AiSIS will advance the study of molecular mechanisms causing singularity phenomena.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211018"},"PeriodicalIF":1.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038667","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}

引用次数: 0

X-ray diffraction recording from a small amount of fibrous protein materials oriented by a micro shear-flow cell. 通过微型剪切流池定向的少量纤维蛋白质材料的 X 射线衍射记录。

IF 1.6

Biophysics and physicobiology Pub Date : 2024-04-20 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0014

Hiroyuki Iwamoto, Kazuhiro Oiwa, Kogiku Shiba, Kazuo Inaba

引用次数: 0

Optimizing tumor treating fields for blood cancer therapy: Analysis of electric field distribution and dose density. 优化血癌治疗的肿瘤治疗场：电场分布和剂量密度分析

IF 1.6

Biophysics and physicobiology Pub Date : 2024-04-18 eCollection Date: 2024-01-01 DOI: 10.2142/biophysico.bppb-v21.0013

Nasori Nasori, Miftakhul Firdhaus, Ulya Farahdina, Rini Khamimatul Ula

{"title":"Optimizing tumor treating fields for blood cancer therapy: Analysis of electric field distribution and dose density.","authors":"Nasori Nasori, Miftakhul Firdhaus, Ulya Farahdina, Rini Khamimatul Ula","doi":"10.2142/biophysico.bppb-v21.0013","DOIUrl":"https://doi.org/10.2142/biophysico.bppb-v21.0013","url":null,"abstract":"Blood cancer is a condition in which white blood cells grow uncontrollably. Tumor treating fields (TTF) are a modality of cancer treatment that utilizes electric fields to target malignant cells. To optimize the efficacy of TTF, it is necessary to investigate the distribution of electric field through varying electrode configurations and input parameters. This allows for enhancement of electric field intensity in targeted areas while minimizing intensity in sensitive areas. Analysis of electric field distribution was conducted through simulation of brachial models with varying electrode configurations and input parameters, utilizing the COMSOL Multiphysics 5.4 software. Additionally, investigations were carried out to assess tissue dose density. The dose density value at primary target for all electrode configurations and input parameters do not exceed the threshold value (770 W/m3), whereas the electric field value at the primary target satisfied the threshold value (100 V/m) on the system that used 4 plate-shaped electrodes and arm contour-shaped electrodes with an input voltage of 20 V, and at the input voltage 15 V, only 4 arm contour-shaped electrodes that satisfied the threshold value. An increase in input voltage, electrodes addition, and electrodes adjustment to skin contour shape result in an enhancement of electric field distribution and average electric field value at primary targets.","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 2","pages":"e210013"},"PeriodicalIF":1.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116819","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}

引用次数: 0