Biophysical journal最新文献_第10页

Prediction Accuracy of Ligand Binding Kinetics. 配体结合动力学的预测精度。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-03-18 DOI: 10.1016/j.bpj.2026.03.033

Fu Xiao,Yinglong Miao

引用次数: 0

Multi-dataset Bayesian analysis synergistically boosts ITC parameter precision. 多数据集贝叶斯分析协同提高ITC参数精度。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-03-18 DOI: 10.1016/j.bpj.2026.03.031

Lisa Otten,Douglas R Walker,Elisar J Barbar,Daniel M Zuckerman

{"title":"Multi-dataset Bayesian analysis synergistically boosts ITC parameter precision.","authors":"Lisa Otten,Douglas R Walker,Elisar J Barbar,Daniel M Zuckerman","doi":"10.1016/j.bpj.2026.03.031","DOIUrl":"https://doi.org/10.1016/j.bpj.2026.03.031","url":null,"abstract":"Isothermal titration calorimetry (ITC) is a powerful technique for probing biomolecular interactions. However, accurate and precise determination of binding parameters-such as enthalpy and free energy, as well as associated uncertainties-can be hindered by noise and concentration variability. In particular, the recently noted mathematical ambiguity surrounding analyte concentrations intrinsically limits the precision with which binding parameters can be determined. Here, we compare several Bayesian approaches to validate a pipeline that resolves this ambiguity by combining two key strategies: simultaneous analysis of multiple ITC datasets and a hierarchical Bayesian treatment of analyte concentration priors. Together, these strategies lift the degeneracy inherent in single-dataset studies and remove an ambiguity typically present in Bayesian analysis by self-consistently refining concentration estimates. This enables optimal joint inference of binding parameters and concentrations, while delivering a precision gain that surpasses conventional square-root-of-n averaging expectations through hierarchical information sharing across datasets. Leveraging modern Monte Carlo methods, our pipeline performs robust posterior sampling for more than 10 datasets and 40 total parameters. We validate the framework with synthetic ITC datasets for single- and multi-site binding models and demonstrate its utility on experimental data, including 14 datasets for 1:1 binding of Mg(II) to the chelator EDTA and four datasets of the hub protein LC8 with its binding partner VP35. This work serves as a foundation for improving the precision of binding constants using multiple ITC datasets, while providing a systematic framework for assessing the reliability of experimental concentration estimates, paving the way for more accurate biomolecular interaction studies.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"60 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478550","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}

引用次数: 0

Mapping bidirectional allosteric communication in Arf GTPases. 在arfgtp酶中映射双向变构通信。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2026-03-17 Epub Date: 2026-02-12 DOI: 10.1016/j.bpj.2026.02.009

Edgar V Peters, Tejaswi Koduru, Scott A McCallum, Estella F Yee, Jacqueline Cherfils, Catherine A Royer

{"title":"Mapping bidirectional allosteric communication in Arf GTPases.","authors":"Edgar V Peters, Tejaswi Koduru, Scott A McCallum, Estella F Yee, Jacqueline Cherfils, Catherine A Royer","doi":"10.1016/j.bpj.2026.02.009","DOIUrl":"10.1016/j.bpj.2026.02.009","url":null,"abstract":"The Arf GTPases are eukaryotic signaling proteins implicated in trafficking, motility, and membrane remodeling. They must undergo a massive conformational transition in the switch between their inactive, GDP-bound form and their GTP-bound form, competent for downstream signaling. The mechanism of their GDP-to-GTP nucleotide switch implicates a functional molten globule (MG) ensemble. Access to this ensemble and apparent spontaneous switching is modulated by residues in the C-terminal half of the different Arf homologs through a \"back-to-front\" allosteric pathway. Here, using high pressure (HP) NMR we show that a mutation in the N-terminal switch region in the front of Arf1 known to modulate spontaneous switching perturbs the stability of residues on a path that stretches from the \"front\" to the \"back.\" This confirms the existence of a continuous allosteric pathway that runs from back to the front and vice versa through the GDP ligand. HP switching studies also demonstrate that the allosteric mechanism controls access to the functional MG state, rather than directly affecting the switching rates.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1506-1515"},"PeriodicalIF":3.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194002","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}

引用次数: 0

Backbone rigidity encodes universal viscoelastic signatures in biomolecular condensates. 主干刚度编码生物分子凝聚物的普遍粘弹性特征。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2026-03-17 Epub Date: 2026-02-04 DOI: 10.1016/j.bpj.2026.01.051

Sean Yang, Subhadip Biswas, Davit A Potoyan

{"title":"Backbone rigidity encodes universal viscoelastic signatures in biomolecular condensates.","authors":"Sean Yang, Subhadip Biswas, Davit A Potoyan","doi":"10.1016/j.bpj.2026.01.051","DOIUrl":"10.1016/j.bpj.2026.01.051","url":null,"abstract":"Biomolecular condensates exhibit a wide range of viscoelastic properties, shaped by their molecular grammar and composition. Coarse-grained molecular models of biomolecules are widely used to complement experiments for revealing the molecular drivers of thermodynamic stability and dynamics. However, fully flexible chain representations of proteins used in widely popular models often fail to capture their complex viscoelastic dynamics, instead predicting purely viscous responses. In this work, we demonstrate that introducing sequence-dependent chain rigidity enables us to quantitatively reproduce the experimentally observed viscelasticity trends for the low complexity domain of hnRNPA1 protein (A1-LCD) condensates and their variants. Furthermore, we show that the frequency-dependent loss factor can be characterized by a single descriptor that correlates with viscosity across A1-LCD variants and diverse parameter settings within a single-bead, semiflexible coarse-grained model. We further find that increasing backbone rigidity expands the elastic-dominated frequency range and is accompanied by more extended condensate-phase conformations. Finally, we elucidate the microscopic origins of sequence-encoded viscoelasticity by demonstrating how it can be tuned through sequence rearrangements that promote the formation of sticker clusters.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1434-1444"},"PeriodicalIF":3.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123216","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}

引用次数: 0

Lattice instability drives formation of protofilament clusters at the microtubule plus-end tips. 晶格不稳定性驱动微管+端尖端原丝团簇的形成。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2026-03-17 Epub Date: 2026-02-14 DOI: 10.1016/j.bpj.2026.02.013

Weizhi Xue, Jiangbo Wu, Tamara Bidone, Gregory A Voth

{"title":"Lattice instability drives formation of protofilament clusters at the microtubule plus-end tips.","authors":"Weizhi Xue, Jiangbo Wu, Tamara Bidone, Gregory A Voth","doi":"10.1016/j.bpj.2026.02.013","DOIUrl":"10.1016/j.bpj.2026.02.013","url":null,"abstract":"Microtubules (MTs) are dynamic cytoskeletal filaments composed of α- and β-tubulin protein dimers. They are crucial for maintaining cell structure, facilitating intracellular transport, and ensuring proper chromosome segregation among other things. These biological functions are influenced by the dynamic instability of the MT plus-end tip. Recent simulations have discovered formation of protofilament (PF) clusters at the MT plus-end tip, but reliable extrapolation of PF cluster dynamics and detailed microscopic mechanism are still needed to understand their behavior thoroughly. In this work, we have constructed, from \"bottom up,\" a relatively high-resolution coarse-grained (CG) molecular dynamics (MD) model for tubulins with 20 CG sites per tubulin monomer, performed extensive CG MD simulations on MT lattices with 8 and 40 layers of heterodimers, and conducted comprehensive atomistic-level analysis. Our findings demonstrate that, in both GTP and GDP states, PF clusters are stable up to tens of microseconds of CG MD simulation time during spontaneous outward bending relaxation. PF clustering is initiated by longitudinal relaxation, stabilized by residual lateral interaction in the PF clusters. This process is thermodynamically driven by intrinsic lattice instability. In longer microtubules, this instability accumulates and further facilitates PF bending and clustering at the plus-end tip, but it can also be released via lattice curvature and supertwist. GDP-MTs form more PF clusters than GTP-MT on average and undergo more lateral cleavage and faster bending relaxation due to weaker lateral interactions, which facilitates MT catastrophe. GTP-MT forms flatter and more rigid PF clusters that favor nucleotide addition. Our findings highlight the critical role of lattice instability in microtubule dynamics and offer new insights on the conformational variability of MT plus-end tips.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1516-1531"},"PeriodicalIF":3.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13023998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197149","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}

引用次数: 0

Distinct allosteric paths mediate a Ca²⁺-dependent increase in NMDA receptor sensitivity to open-channel blockers. 不同的变构途径介导Ca2+依赖性的NMDA受体对开放通道阻滞剂的敏感性增加。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2026-03-17 Epub Date: 2026-02-04 DOI: 10.1016/j.bpj.2026.02.002

Mae G Weaver, Jamie A Abbott, Gabriela K Popescu

{"title":"Distinct allosteric paths mediate a Ca2+-dependent increase in NMDA receptor sensitivity to open-channel blockers.","authors":"Mae G Weaver, Jamie A Abbott, Gabriela K Popescu","doi":"10.1016/j.bpj.2026.02.002","DOIUrl":"10.1016/j.bpj.2026.02.002","url":null,"abstract":"When active, NMDA receptors pass Ca2+-rich excitatory currents that are essential for the normal development and function of the central nervous system. In turn, fluctuations in extracellular Ca2+ levels, as observed during synaptic activity and pathological states, affect the NMDA receptor gating kinetics and conductance. Here, we used patch-clamp electrophysiology, kinetic analyses, and mutagenesis to evaluate how changes in the ambient Ca2+ concentration affect the sensitivity of recombinant NMDA receptors to open-channel blockers. NMDA receptor currents are characteristically sensitive to voltage-dependent block by Mg2+, which endows them physiologically with coincidence detection. This regulatory mechanism is shared with ketamine and memantine, two synthetic compounds that are clinically effective for treating depression and Alzheimer's disease, respectively. We found that extracellular Ca2+ increased the sensitivity of NMDA receptors to block by Mg2+ and memantine but not by ketamine. Further, the effect of Ca2+ on block by memantine required intracellular Ca2+ and functional calmodulin, whereas the effect of Ca2+ on block by Mg2+ required the extracellular residue GluN1-D658. We conclude that extracellular Ca2+ fluctuations modulate the sensitivity of NMDA receptors to open-channel blockers by discrete mechanisms, which may explain the distinct clinical profiles of NMDA receptor blockers.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1456-1463"},"PeriodicalIF":3.1,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123222","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}

引用次数: 0

Disruption of nuclear-cytoskeletal connection impairs epithelial cell mechanosensing and collective migration 核-细胞骨架连接的破坏会损害上皮细胞的机械感知和集体迁移

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-03-14 DOI: 10.1016/j.bpj.2026.03.030

Akash T. Shaji, Amit Pathak

引用次数: 0

Conformational Flexibility and Transient Structure of the Proline-Rich Domain in p53 p53富含脯氨酸结构域的构象灵活性和瞬时结构

IF 3.4 3区生物学

Biophysical journal Pub Date : 2026-03-14 DOI: 10.1016/j.bpj.2026.03.024

Agnes Berggren, Michael Bakker, Hayden Fisher, Marie Skepö

引用次数: 0

Biophysical and Structural Analysis of Human Green Cone Opsin (GCO). 人体绿锥视蛋白（GCO）的生物物理和结构分析。