Biophysics and Physicobiology最新文献_第2页

Quantitative analysis of protein dynamics using a deep learning technique combined with experimental cryo-EM density data and MD simulations. 利用深度学习技术结合实验性低温电子显微镜密度数据和 MD 模拟对蛋白质动力学进行定量分析。

Biophysics and Physicobiology Pub Date : 2023-05-16 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0022

Shigeyuki Matsumoto, Shoichi Ishida, Kei Terayama, Yasuhshi Okuno

{"title":"Quantitative analysis of protein dynamics using a deep learning technique combined with experimental cryo-EM density data and MD simulations.","authors":"Shigeyuki Matsumoto, Shoichi Ishida, Kei Terayama, Yasuhshi Okuno","doi":"10.2142/biophysico.bppb-v20.0022","DOIUrl":"10.2142/biophysico.bppb-v20.0022","url":null,"abstract":"Protein functions associated with biological activity are precisely regulated by both tertiary structure and dynamic behavior. Thus, elucidating the high-resolution structures and quantitative information on in-solution dynamics is essential for understanding the molecular mechanisms. The main experimental approaches for determining tertiary structures include nuclear magnetic resonance (NMR), X-ray crystallography, and cryogenic electron microscopy (cryo-EM). Among these procedures, recent remarkable advances in the hardware and analytical techniques of cryo-EM have increasingly determined novel atomic structures of macromolecules, especially those with large molecular weights and complex assemblies. In addition to these experimental approaches, deep learning techniques, such as AlphaFold 2, accurately predict structures from amino acid sequences, accelerating structural biology research. Meanwhile, the quantitative analyses of the protein dynamics are conducted using experimental approaches, such as NMR and hydrogen-deuterium mass spectrometry, and computational approaches, such as molecular dynamics (MD) simulations. Although these procedures can quantitatively explore dynamic behavior at high resolution, the fundamental difficulties, such as signal crowding and high computational cost, greatly hinder their application to large and complex biological macromolecules. In recent years, machine learning techniques, especially deep learning techniques, have been actively applied to structural data to identify features that are difficult for humans to recognize from big data. Here, we review our approach to accurately estimate dynamic properties associated with local fluctuations from three-dimensional cryo-EM density data using a deep learning technique combined with MD simulations.","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76574180","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

Phone2SAS: 3D scanning by smartphone aids the realization of small-angle scattering. Phone2SAS：通过智能手机进行三维扫描，帮助实现小角散射。

Biophysics and Physicobiology Pub Date : 2023-05-10 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0021

Hiroshi Imamura

引用次数: 0

Mathematical model of structural changes in nuclear speckle. 核斑点结构变化的数学模型。

Biophysics and Physicobiology Pub Date : 2023-04-27 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0020

Shingo Wakao, Noriko Saitoh, Akinori Awazu

{"title":"Mathematical model of structural changes in nuclear speckle.","authors":"Shingo Wakao, Noriko Saitoh, Akinori Awazu","doi":"10.2142/biophysico.bppb-v20.0020","DOIUrl":"10.2142/biophysico.bppb-v20.0020","url":null,"abstract":"Nuclear speckles are nuclear bodies consisting of populations of small and irregularly shaped droplet-like molecular condensates that contain various splicing factors. Recent experiments have revealed the following structural features of nuclear speckles: (I) Each molecular condensate contains SON and SRRM2 proteins, and MALAT1 non-coding RNA surrounds these condensates; (II) During normal interphase of the cell cycle in multicellular organisms, these condensates are broadly distributed throughout the nucleus. In contrast, when cell transcription is suppressed, the condensates fuse and form strongly condensed spherical droplets; (III) SON is dispersed spatially in MALAT1 knocked-down cells and MALAT1 is dispersed in SON knocked-down cells because of the collapse of the nuclear speckles. However, the detailed interactions among the molecules that are mechanistically responsible for the structural variation remain unknown. In this study, a coarse-grained molecular dynamics model of the nuclear speckle was developed by considering the dynamics of SON, SRRM2, MALAT1, and pre-mRNA as representative components of the condensates. The simulations reproduced the structural changes, which were used to predict the interaction network among the representative components of the condensates.","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76513698","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

Controlling complex dynamical systems based on the structure of the networks. 根据网络结构控制复杂的动力系统。

Biophysics and Physicobiology Pub Date : 2023-04-21 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0019

Atsushi Mochizuki

{"title":"Controlling complex dynamical systems based on the structure of the networks.","authors":"Atsushi Mochizuki","doi":"10.2142/biophysico.bppb-v20.0019","DOIUrl":"10.2142/biophysico.bppb-v20.0019","url":null,"abstract":"Progress of molecular biology resulted in the accumulation of information on biomolecular interactions, which are complex enough to be termed as networks. Dynamical behavior generated by complex network systems is considered to be the origin of the biological functions. One of the largest missions in modern life science is to obtain logical understanding for the dynamics of complex systems based on experimentally identified networks. However, a network does not provide sufficient information to specify dynamics explicitly, i.e. it lacks information of mathematical formulae of functions or parameter values. One has to develop mathematical models under assumptions of functions and parameter values to know the detail of dynamics of network systems. In this review, on the other hand, we introduce our own mathematical theory to understand the behavior of biological systems from the information of regulatory networks alone. Using the theory, important aspects of dynamical properties can be extracted from networks. Namely, key factors for observing/controlling the whole dynamical system are determined from network structure alone. We also show an application of the theory to a real biological system, a gene regulatory network for cell-fate specification in ascidian. We demonstrate that the system was completely controllable by experimental manipulations of the key factors identified by the theory from the information of network alone. This review article is an extended version of the Japanese article, Controlling Cell-Fate Specification System Based on a Mathematical Theory of Network Dynamics, published in SEIBUTSU BUTSURI Vol. 60, p. 349-351 (2020).","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83572043","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

Guideline for design of substrate stiffness for mesenchymal stem cell culture based on heterogeneity of YAP and RUNX2 responses. 基于 YAP 和 RUNX2 反应异质性的间充质干细胞培养基质硬度设计指南。

Biophysics and Physicobiology Pub Date : 2023-04-19 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0018

Hiromi Miyoshi, Masashi Yamazaki, Hiromichi Fujie, Satoru Kidoaki

{"title":"Guideline for design of substrate stiffness for mesenchymal stem cell culture based on heterogeneity of YAP and RUNX2 responses.","authors":"Hiromi Miyoshi, Masashi Yamazaki, Hiromichi Fujie, Satoru Kidoaki","doi":"10.2142/biophysico.bppb-v20.0018","DOIUrl":"10.2142/biophysico.bppb-v20.0018","url":null,"abstract":"Mesenchymal stem cells (MSCs) have the potential for self-renewal and multipotency to differentiate into various lineages. Thus, they are of great interest in regenerative medicine as a cell source for tissue engineering. Substrate stiffness is one of the most extensively studied exogenous physical factors; however, consistent results have not always been reported for controlling MSCs. Conventionally used stiff culture substrates, such as tissue-culture polystyrene and glass, enhance nuclear localization of a mechanotransducer YAP and a pre-osteogenic transcription factor RUNX2, and bias MSCs towards the osteogenic lineage, even without osteogenic-inducing soluble factors. The mechanosensitive nature and intrinsic heterogeneity present challenges for obtaining reproducible results. This review summarizes the heterogeneity in human MSC response, specifically, nuclear/cytoplasmic localization changes in the mechanotransducer yes-associated protein (YAP) and the osteogenic transcription factor RUNX2, in response to substrate stiffness. In addition, a perspective on the intracellular factors attributed to response heterogeneity is discussed. The optimal range of stiffness parameters, Young's modulus, for MSC expansion culture to suppress osteogenic differentiation bias through the suppression of YAP and RUNX2 nuclear localization, and cell cycle progression is likely to be surprisingly narrow for a cell population from an identical donor and vary among cell populations from different donors. We believe that characterization of the heterogeneity of MSCs and understanding their biological meaning is an exciting research direction to establish guidelines for the design of culture substrates for the sophisticated control of MSC properties.","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82322641","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

Identification and structural basis of an enzyme that degrades oligosaccharides in caramel. 鉴定一种降解焦糖中低聚糖的酶及其结构基础。

Biophysics and Physicobiology Pub Date : 2023-03-29 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0017

Toma Kashima, Akihiro Ishiwata, Kiyotaka Fujita, Shinya Fushinobu

{"title":"Identification and structural basis of an enzyme that degrades oligosaccharides in caramel.","authors":"Toma Kashima, Akihiro Ishiwata, Kiyotaka Fujita, Shinya Fushinobu","doi":"10.2142/biophysico.bppb-v20.0017","DOIUrl":"10.2142/biophysico.bppb-v20.0017","url":null,"abstract":"Cooking with fire produces foods containing carbohydrates that are not naturally occurring, such as α-d-fructofuranoside found in caramel. Each of the hundreds of compounds produced by caramelization reactions is considered to possess its own characteristics. Various studies from the viewpoints of biology and biochemistry have been conducted to elucidate some of the scientific characteristics. Here, we review the composition of caramelized sugars and then describe the enzymatic studies that have been conducted and the physiological functions of the caramelized sugar components that have been elucidated. In particular, we recently identified a glycoside hydrolase (GH), GH172 difructose dianhydride I synthase/hydrolase (αFFase1), from oral and intestinal bacteria, which is implicated in the degradation of oligosaccharides in caramel. The structural basis of αFFase1 and its ligands provided many insights. This discovery opened the door to several research fields, including the structural and phylogenetic relationship between the GH172 family enzymes and viral capsid proteins and the degradation of cell membrane glycans of acid-fast bacteria by some αFFase1 homologs. This review article is an extended version of the Japanese article, Identification and Structural Basis of an Enzyme Degrading Oligosaccharides in Caramel, published in SEIBUTSU BUTSURI Vol. 62, p. 184-186 (2022).","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76796845","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

Calculations of the binding free energies of the Comprehensive in vitro Proarrhythmia Assay (CiPA) reference drugs to cardiac ion channels. 计算体外原发性心律失常综合分析（CiPA）参考药物与心脏离子通道的结合自由能。

Biophysics and Physicobiology Pub Date : 2023-03-25 eCollection Date: 2023-01-01 DOI: 10.2142/biophysico.bppb-v20.0016

Tatsuki Negami, Tohru Terada

{"title":"Calculations of the binding free energies of the Comprehensive in vitro Proarrhythmia Assay (CiPA) reference drugs to cardiac ion channels.","authors":"Tatsuki Negami, Tohru Terada","doi":"10.2142/biophysico.bppb-v20.0016","DOIUrl":"10.2142/biophysico.bppb-v20.0016","url":null,"abstract":"The evaluation of the inhibitory activities of drugs on multiple cardiac ion channels is required for the accurate assessment of proarrhythmic risks. Moreover, the in silico prediction of such inhibitory activities of drugs on cardiac channels can improve the efficiency of the drug-development process. Here, we performed molecular docking simulations to predict the complex structures of 25 reference drugs that were proposed by the Comprehensive in vitro Proarrhythmia Assay consortium using two cardiac ion channels, the human ether-a-go-go-related gene (hERG) potassium channel and human NaV1.5 (hNaV1.5) sodium channel, with experimentally available structures. The absolute binding free energy (ΔGbind) values of the predicted structures were calculated by a molecular dynamics-based method and compared with the experimental half-maximal inhibitory concentration (IC50) data. Furthermore, the regression analysis between the calculated values and negative of the common logarithm of the experimental IC50 values (pIC50) revealed that the calculated values of four and ten drugs deviated significantly from the regression lines of the hERG and hNaV1.5 channels, respectively. We reconsidered the docking poses and protonation states of the drugs based on the experimental data and recalculated their ΔGbind values. Finally, the calculated ΔGbind values of 24 and 19 drugs correlated with their experimental pIC50 values (coefficients of determination=0.791 and 0.613 for the hERG and hNaV1.5 channels, respectively). Thus, the regression analysis between the calculated ΔGbind and experimental IC50 data ensured the realization of an increased number of reliable complex structures.","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83917689","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

Biophysical characterization of microbial rhodopsins with DSE motif. 具有 DSE 基调的微生物荷尔蒙蛋白的生物物理特征。

Biophysics and Physicobiology Pub Date : 2023-03-08 eCollection Date: 2023-03-21 DOI: 10.2142/biophysico.bppb-v20.s023

María Del Carmen Marín, Alexander L Jaffe, Patrick T West, Masae Konno, Jillian F Banfield, Keiichi Inoue

{"title":"Biophysical characterization of microbial rhodopsins with DSE motif.","authors":"María Del Carmen Marín, Alexander L Jaffe, Patrick T West, Masae Konno, Jillian F Banfield, Keiichi Inoue","doi":"10.2142/biophysico.bppb-v20.s023","DOIUrl":"10.2142/biophysico.bppb-v20.s023","url":null,"abstract":"Microbial rhodopsins are photoreceptive transmembrane proteins that transport ions or regulate other intracellular biological processes. Recent genomic and metagenomic analyses found many microbial rhodopsins with unique sequences distinct from known ones. Functional characterization of these new types of microbial rhodopsins is expected to expand our understanding of their physiological roles. Here, we found microbial rhodopsins having a DSE motif in the third transmembrane helix from members of the Actinobacteria. Although the expressed proteins exhibited blue-green light absorption, either no or extremely small outward H+ pump activity was observed. The turnover rate of the photocycle reaction of the purified proteins was extremely slow compared to typical H+ pumps, suggesting these rhodopsins would work as photosensors or H+ pumps whose activities are enhanced by an unknown regulatory system in the hosts. The discovery of this rhodopsin group with the unique motif and functionality expands our understanding of the biological role of microbial rhodopsins.","PeriodicalId":8976,"journal":{"name":"Biophysics and Physicobiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82939535","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

Introduction of Session 2, "Advanced methods for retinal proteins". 介绍分会 2 "视网膜蛋白质的先进方法"。

Biophysics and Physicobiology Pub Date : 2023-03-07 eCollection Date: 2023-03-21 DOI: 10.2142/biophysico.bppb-v20.s022

Takayuki Uchihashi, Hideki Kandori

引用次数: 0

Introduction of Session 1, "Photochemistry of retinal proteins". 介绍分会 1 "视网膜蛋白质的光化学"。

Biophysics and Physicobiology Pub Date : 2023-03-04 eCollection Date: 2023-03-21 DOI: 10.2142/biophysico.bppb-v20.s021

Yuki Sudo

引用次数: 0