Journal of Biological Physics最新文献_第9页

Thermodynamics of unfolding mechanisms of mouse mammary tumor virus pseudoknot from a coarse-grained loop-entropy model 基于粗粒度环熵模型的小鼠乳腺肿瘤病毒假结展开机制的热力学研究

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-04-20 DOI: 10.1007/s10867-022-09602-2

Ke Tang, Jorjethe Roca, Rong Chen, Anjum Ansari, Jie Liang

{"title":"Thermodynamics of unfolding mechanisms of mouse mammary tumor virus pseudoknot from a coarse-grained loop-entropy model","authors":"Ke Tang, Jorjethe Roca, Rong Chen, Anjum Ansari, Jie Liang","doi":"10.1007/s10867-022-09602-2","DOIUrl":"10.1007/s10867-022-09602-2","url":null,"abstract":"<div><p>Pseudoknotted RNA molecules play important biological roles that depend on their folded structure. To understand the underlying principles that determine their thermodynamics and folding/unfolding mechanisms, we carried out a study on a variant of the mouse mammary tumor virus pseudoknotted RNA (VPK), a widely studied model system for RNA pseudoknots. Our method is based on a coarse-grained discrete-state model and the algorithm of PK3D (pseudoknot structure predictor in three-dimensional space), with RNA loops explicitly constructed and their conformational entropic effects incorporated. Our loop entropy calculations are validated by accurately capturing previously measured melting temperatures of RNA hairpins with varying loop lengths. For each of the hairpins that constitutes the VPK, we identified alternative conformations that are more stable than the hairpin structures at low temperatures and predicted their populations at different temperatures. Our predictions were validated by thermodynamic experiments on these hairpins. We further computed the heat capacity profiles of VPK, which are in excellent agreement with available experimental data. Notably, our model provides detailed information on the unfolding mechanisms of pseudoknotted RNA. Analysis of the distribution of base-pairing probability of VPK reveals a cooperative unfolding mechanism instead of a simple sequential unfolding of first one stem and then the other. Specifically, we find a simultaneous “loosening” of both stems as the temperature is raised, whereby both stems become partially melted and co-exist during the unfolding process.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 2","pages":"129 - 150"},"PeriodicalIF":1.8,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-022-09602-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4783428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantification of adaptive forces on SNP rs1010211 due to viral zoonotic pathogens 病毒性人畜共患病原体对SNP rs1010211的适应性的定量分析

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-04-15 DOI: 10.1007/s10867-022-09606-y

Daniah Alsufyani, James Lindesay

{"title":"Quantification of adaptive forces on SNP rs1010211 due to viral zoonotic pathogens","authors":"Daniah Alsufyani, James Lindesay","doi":"10.1007/s10867-022-09606-y","DOIUrl":"10.1007/s10867-022-09606-y","url":null,"abstract":"<div><p>Widespread genotyping of human populations in environmental homeostasis has created opportunities to quantify how environmental parameters affect the genomic distribution of variants in healthy populations. This represents an ongoing natural experiment upon the human species that can only be understood through developing models of adaptation. By examining the information dynamics of optimal SNP distributions within such populations, “adaptive forces” on genomic variants can be quantified through comparisons between different populations. To this end, we are performing double-blind scans of SNPs in order to ascertain any potential smooth functional relationships between the frequencies of the variants and changes in quantified environmental parameters. At present, we have sequentially examined more than twenty thousand SNPs (on chromosome 3) of nine homeostatic native populations for potential adaptive flagging of the variants as functions of 15 environmental parameters. Our first significant flag has related rs1010211 to viral pathogens in mammalian hosts. Such pathogens present a significant risk for the emergence of new infectious diseases in humans. This genomic variant is within the gene TNIK, which is a germinal center kinase (GCK). GCKs are participants in both adaptive and innate immune regulation. However, the function of TNIK is not fully understood. We quantify the adaptive force on the C allele due to the pathogens as 0.04 GEU’s/viral species.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 2","pages":"227 - 236"},"PeriodicalIF":1.8,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-022-09606-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4594050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Modulation of free energy landscapes as a strategy for the design of antimicrobial peptides 自由能景观的调节作为抗菌肽设计的一种策略

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-04-14 DOI: 10.1007/s10867-022-09605-z

Sergio A. Hassan, Peter J. Steinbach

{"title":"Modulation of free energy landscapes as a strategy for the design of antimicrobial peptides","authors":"Sergio A. Hassan, Peter J. Steinbach","doi":"10.1007/s10867-022-09605-z","DOIUrl":"10.1007/s10867-022-09605-z","url":null,"abstract":"<div><p>Computational design of antimicrobial peptides (AMPs) is a promising area of research for developing novel agents against drug-resistant bacteria. AMPs are present naturally in many organisms, from bacteria to humans, a time-tested mechanism that makes them attractive as effective antibiotics. Depending on the environment, AMPs can exhibit α-helical or β-sheet conformations, a mix of both, or lack secondary structure; they can be linear or cyclic. Prediction of their structures is challenging but critical for rational design. Promising AMP leads can be developed using essentially two approaches: traditional modeling of the physicochemical mechanisms that determine peptide behavior in aqueous and membrane environments and knowledge-based, e.g., machine learning (ML) techniques, that exploit ever-growing AMP databases. Here, we explore the conformational landscapes of two recently ML-designed AMPs, characterize the dependence of these landscapes on the medium conditions, and identify features in peptide and membrane landscapes that mediate protein-membrane association. For both peptides, we observe greater conformational diversity in an aqueous solvent than in a less polar solvent, and one peptide is seen to alter its conformation more dramatically than the other upon the change of solvent. Our results support the view that structural rearrangement in response to environmental changes is central to the mechanism of membrane-structure disruption by linear peptides. We expect that the design of AMPs by ML will benefit from the incorporation of peptide conformational substates as quantified here with molecular simulations.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 2","pages":"151 - 166"},"PeriodicalIF":1.8,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-022-09605-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4562413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Interaction among bovine serum albumin (BSA) molecules in the presence of anions: a small-angle neutron scattering study 阴离子存在下牛血清白蛋白(BSA)分子间的相互作用:小角中子散射研究

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-04-13 DOI: 10.1007/s10867-022-09608-w

Subhankar Pandit, Sarathi Kundu, Vinod K. Aswal

引用次数: 1

Investigation of extracellular medium osmolality depending on zinc application and incubation time on A549 cancer cells 锌对A549癌细胞胞外介质渗透压影响的研究

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-03-24 DOI: 10.1007/s10867-022-09604-0

Duygu Tarhan, Nural Pastaci Özsobaci, Dilek Düzgün Ergün, Alev Meltem Ercan

{"title":"Investigation of extracellular medium osmolality depending on zinc application and incubation time on A549 cancer cells","authors":"Duygu Tarhan, Nural Pastaci Özsobaci, Dilek Düzgün Ergün, Alev Meltem Ercan","doi":"10.1007/s10867-022-09604-0","DOIUrl":"10.1007/s10867-022-09604-0","url":null,"abstract":"<div><p>Changes in the osmolality of the extracellular medium (ECM) affect cell volume and cellular processes such as cell migration and proliferation. Not only may high concentrations of zinc (Zn) lead to cell death by apoptosis, but Zn is also a physiological suppressor of apoptosis. The aim of our study was to examine whether Zn and regulation of extracellular osmolality had an effect on the lung cancer cell line (A549) and how to be changed in ECM according to elements and osmolality depending on incubation time and Zn application. Our study consisted of four groups: cell-free medium, ECM of cancer cell after 24 h incubation (24hECM), ECM of cancer cell after 48 h incubation (48hECM), and ECM of cancer cell after 48 h incubation with ZnCl<sub>2</sub> (48hECM + Zn). ECM osmolality was measured by using osmometer, and the levels of chromium (Cr), iron (Fe), and magnesium (Mg) elements were analyzed using ICP-OES device for all groups. According to the result of the analysis, a statistically significant difference was found when osmolality and element values of ECM of 24hECM and 48hECM groups were compared with the values of the 48hECM + Zn group. It was observed that there was a decrease in the levels of Cr, Fe, and Mg with Zn application and incubation period in ECM. The regulation of ECM osmolality is a promising method due to biophysical effects on cancer cells. In our study, we speculated that the understanding of the effects of Zn and osmolality with the relationship between ECM and cancer cell might lead to the discovery of biophysical approaches as a novel therapeutic strategy.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 2","pages":"215 - 226"},"PeriodicalIF":1.8,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-022-09604-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4943552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A neurocomputational model for the processing of conflicting information in context-dependent decision tasks 情境依赖决策任务中冲突信息处理的神经计算模型

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-03-08 DOI: 10.1007/s10867-021-09601-9

Francisco M. López, Andrés Pomi

{"title":"A neurocomputational model for the processing of conflicting information in context-dependent decision tasks","authors":"Francisco M. López, Andrés Pomi","doi":"10.1007/s10867-021-09601-9","DOIUrl":"10.1007/s10867-021-09601-9","url":null,"abstract":"<div><p>Context-dependent computation is a relevant characteristic of neural systems, endowing them with the capacity of adaptively modifying behavioral responses and flexibly discriminating between relevant and irrelevant information in a stimulus. This ability is particularly highlighted in solving conflicting tasks. A long-standing problem in computational neuroscience, flexible routing of information, is also closely linked with the ability to perform context-dependent associations. Here we present an extension of a context-dependent associative memory model to achieve context-dependent decision-making in the presence of conflicting and noisy multi-attribute stimuli. In these models, the input vectors are multiplied by context vectors via the Kronecker tensor product. To outfit the model with a noisy dynamic, we embedded the context-dependent associative memory in a leaky competing accumulator model, and, finally, we proved the power of the model in the reproduction of a behavioral experiment with monkeys in a context-dependent conflicting decision-making task. At the end, we discuss the neural feasibility of the tensor product and made the suggestive observation that the capacities of tensor context models are surprisingly in alignment with the more recent experimental findings about functional flexibility at different levels of brain organization.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 2","pages":"195 - 213"},"PeriodicalIF":1.8,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-021-09601-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4346787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Study of β-lactam-based drug interaction with albumin protein using optical, sensing, and docking methods 利用光学、传感和对接方法研究β-内酰胺类药物与白蛋白的相互作用

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-01-30 DOI: 10.1007/s10867-021-09599-0

Hannaneh Monirinasab, Mostafa Zakariazadeh, Havva Kohestani, Morteza Kouhestani, Farzaneh Fathi

{"title":"Study of β-lactam-based drug interaction with albumin protein using optical, sensing, and docking methods","authors":"Hannaneh Monirinasab, Mostafa Zakariazadeh, Havva Kohestani, Morteza Kouhestani, Farzaneh Fathi","doi":"10.1007/s10867-021-09599-0","DOIUrl":"10.1007/s10867-021-09599-0","url":null,"abstract":"<div><p>The quality and strength of drug and albumin interaction affecting the drug-free concentration and physiological activity are important issues in pharmacokinetic research. In the present study, not only did we evaluate the binding strength of ceftriaxone and ceftizoxime to bovine serum albumin (BSA), but we also investigated the kinetic and thermodynamic parameters including KD, KA, ΔS, and ΔH. We applied in vitro optical fluorescence spectroscopy and surface plasmon resonance (SPR) sensing approaches as well as molecular docking analyses. The kinetic and thermodynamic investigations were done using different concentrations of drugs at three temperatures. Thermodynamic parameters visibly demonstrated that the binding was an exothermic and spontaneous process. The obtained negative values of both enthalpy change (ΔH) and entropy change (ΔS) in fluorescence and SPR and also molecular docking investigations showed that the major binding force involved in the complexation of drugs to BSA was hydrogen bonding. Static quenching was the foremost fluorescence quenching mechanism between them. Furthermore, the results of ΔG and <i>K</i><sub><i>D</i></sub> values proved that the interaction of ceftriaxone-BSA was stronger than ceftizoxime-BSA. Finally, molecular docking confirmed that the preferable binding sites of ceftizoxime and ceftriaxone were site IIA and site IB of albumin, respectively.</p><h3>Graphic abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 2","pages":"177 - 194"},"PeriodicalIF":1.8,"publicationDate":"2022-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-021-09599-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4011815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Biological computation: hearts and flytraps 生物计算:心脏和捕蝇器

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-01-28 DOI: 10.1007/s10867-021-09590-9

Kay L. Kirkpatrick

引用次数: 2

The effects of temperature on the dynamics of the biological neural network 温度对生物神经网络动力学的影响

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-01-21 DOI: 10.1007/s10867-021-09598-1

Mohammad B Jabbari, Mahdi Rezaei Karamati

{"title":"The effects of temperature on the dynamics of the biological neural network","authors":"Mohammad B Jabbari, Mahdi Rezaei Karamati","doi":"10.1007/s10867-021-09598-1","DOIUrl":"10.1007/s10867-021-09598-1","url":null,"abstract":"<div><p>The nerve cells are responsible for transmitting messages through the action potential, which generates electrical stimulation. One of the methods and tools of electrical stimulation is infrared neural stimulation (INS). Since the mechanism of INS is based on electromagnetic radiation, it explains how a neuron is stimulated by the heat distribution which is generated by the laser. The present study is focused on modeling and simulating the conditions in which deformed temperature related to the Hodgkin and Huxley model can be effectively and safely used to activate the neurons, the fires of which depend on temperature. The results explain ionic channels in the single and network neurons, which behave differently when thermal stimulation is applied to the cell. It causes the variation of the pattern of the action potential in the Hodgkin-Huxley (HH) model. The stability of the phase-plane at high temperatures has lower fluctuations than at low temperatures, so the channel gates open and close faster. The behavior of these channels under various membrane temperatures shows that the firing rate increases with temperature. Also, the domain of the spikes reduces and the spikes occur faster with increasing temperature.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 1","pages":"111 - 126"},"PeriodicalIF":1.8,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-021-09598-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4820748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model 使用混合awsem -血红素模型探索血红素蛋白的折叠能量景观

IF 1.8 4区生物学

Journal of Biological Physics Pub Date : 2022-01-09 DOI: 10.1007/s10867-021-09596-3

Xun Chen, Wei Lu, Min-Yeh Tsai, Shikai Jin, Peter G. Wolynes

{"title":"Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model","authors":"Xun Chen, Wei Lu, Min-Yeh Tsai, Shikai Jin, Peter G. Wolynes","doi":"10.1007/s10867-021-09596-3","DOIUrl":"10.1007/s10867-021-09596-3","url":null,"abstract":"<div><p>Heme is an active center in many proteins. Here we explore computationally the role of heme in protein folding and protein structure. We model heme proteins using a hybrid model employing the AWSEM Hamiltonian, a coarse-grained forcefield for the protein chain along with AMBER, an all-atom forcefield for the heme. We carefully designed transferable force fields that model the interactions between the protein and the heme. The types of protein–ligand interactions in the hybrid model include thioester covalent bonds, coordinated covalent bonds, hydrogen bonds, and electrostatics. We explore the influence of different types of hemes (heme b and heme c) on folding and structure prediction. Including both types of heme improves the quality of protein structure predictions. The free energy landscape shows that both types of heme can act as nucleation sites for protein folding and stabilize the protein folded state. In binding the heme, coordinated covalent bonds and thioester covalent bonds for heme c drive the heme toward the native pocket. The electrostatics also facilitates the search for the binding site.</p></div>","PeriodicalId":612,"journal":{"name":"Journal of Biological Physics","volume":"48 1","pages":"37 - 53"},"PeriodicalIF":1.8,"publicationDate":"2022-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10867-021-09596-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4386492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2