European Biophysics Journal最新文献

Rational design of potent phosphopeptide binders to endocrine Snk PBD domain by integrating machine learning optimization, molecular dynamics simulation, binding energetics rescoring, and in vitro affinity assay.

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-11-29 DOI: 10.1007/s00249-024-01729-5

Zhaohui Wang, Jixiao Lan, Yan Feng, Yumei Chen, Meiyuan Chen

{"title":"Rational design of potent phosphopeptide binders to endocrine Snk PBD domain by integrating machine learning optimization, molecular dynamics simulation, binding energetics rescoring, and in vitro affinity assay.","authors":"Zhaohui Wang, Jixiao Lan, Yan Feng, Yumei Chen, Meiyuan Chen","doi":"10.1007/s00249-024-01729-5","DOIUrl":"https://doi.org/10.1007/s00249-024-01729-5","url":null,"abstract":"<p><p>Human Snk is an evolutionarily conserved serine/threonine kinase essential for the maintenance of endocrine stability. The protein consists of a N-terminal catalytic domain and a C-terminal polo-box domain (PBD) that determines subcellular localization and substrate specificity. Here, an integrated strategy is described to explore the vast structural diversity space of Snk PBD-binding phosphopeptides at a molecular level using machine learning modeling, annealing optimization, dynamics simulation, and energetics rescoring, focusing on the recognition specificity and motif preference of the Snk PBD domain. We further performed a systematic rational design of potent phosphopeptide ligands for the domain based on the harvested knowledge, from which a few potent binders were also confirmed by fluorescence-based assays. A phosphopeptide PP17 was designed as a good binder with affinity improvement by 6.7-fold relative to the control PP0, while the other three designed phosphopeptides PP7, PP13, and PP15 exhibit a comparable potency with PP0. In addition, a basic recognition motif that divides potent Snk PBD-binding sequences into four residue blocks was defined, namely [Χ<sub>-5</sub>Χ-<sub>4</sub>]<sub>block1</sub>-[Ω<sub>-3</sub>Ω<sub>-2</sub>Ω<sub>-1</sub>]<sub>block2</sub>-[pS<sub>0</sub>/pT<sub>0</sub>]<sub>block3</sub>-[Ψ<sub>+1</sub>]<sub>block4</sub>, where the X represents any amino acid, Ω indicates polar amino acid, Ψ denotes hydrophobic amino acid, and pS<sub>0</sub>/pT<sub>0</sub> is the anchor phosphoserine/phosphothreonine at reference residue position 0.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Exploring characteristic features for effective HCN1 channel inhibition using integrated analytical approaches: 3D QSAR, molecular docking, homology modelling, ADME and molecular dynamics 利用综合分析方法探索有效抑制 HCN1 通道的特征：3D QSAR、分子对接、同源建模、ADME 和分子动力学。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-11-03 DOI: 10.1007/s00249-024-01726-8

Shiwani Sharma, Priyanka Rana, Vijayta Dani Chadha, Neelima Dhingra, Tanzeer Kaur

{"title":"Exploring characteristic features for effective HCN1 channel inhibition using integrated analytical approaches: 3D QSAR, molecular docking, homology modelling, ADME and molecular dynamics","authors":"Shiwani Sharma, Priyanka Rana, Vijayta Dani Chadha, Neelima Dhingra, Tanzeer Kaur","doi":"10.1007/s00249-024-01726-8","DOIUrl":"10.1007/s00249-024-01726-8","url":null,"abstract":"<div><p>Neuropathic pain (NP) is characterized by hyperalgesia, allodynia, and spontaneous pain. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel involved in neuronal hyperexcitability, has emerged as an important target for the drug development of NP. HCN channels exist in four different isoforms, where HCN1 is majorly expressed in dorsal root ganglion having an imperative role in NP pathophysiology. A specific HCN1 channel inhibitor will hold the better potential to treat NP without disturbing the physiological roles of other HCN isoforms. The main objective is to identify and analyze the chemical properties of scaffolds with higher HCN1 channel specificity. The 3D-QSAR studies highlight the hydrophobic & hydrogen bond donor groups enhance specificity towards the HCN1 channel. Further, the molecular interaction of the scaffolds with the HCN1 pore was studied by generating an open-pore model of the HCN1 channel using homology modelling and then docking the molecules with it. In addition, the important residues involved in the interaction between HCN1 pore and scaffolds were also identified. Moreover, ADME predictions revealed that compounds had good oral bioavailability and solubility characteristics. Subsequently, molecular dynamics simulation studies revealed the better stability of the lead molecules A7 and A9 during interactions and ascertained them as potential drug candidates. Cumulative studies provided the important structural features for enhancing HCN1 channel-specific inhibition, paving the way to design and develop novel specific HCN1 channel inhibitors.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"447 - 464"},"PeriodicalIF":2.2,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Quantitative characterization of non-specific interaction of two globular proteins with Dextran T70 in a binary mixture 二元混合物中两种球状蛋白质与右旋糖酐 T70 非特异性相互作用的定量表征。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-10-25 DOI: 10.1007/s00249-024-01727-7

Adedayo A. Fodeke

引用次数: 0

The origin of mutational epistasis 突变外显的起源

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-10-23 DOI: 10.1007/s00249-024-01725-9

Jorge A. Vila

{"title":"The origin of mutational epistasis","authors":"Jorge A. Vila","doi":"10.1007/s00249-024-01725-9","DOIUrl":"10.1007/s00249-024-01725-9","url":null,"abstract":"<div><p>The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin (molecular basis) of epistasis—the non-additive interactions between mutations—is still, nonetheless, unknown. The existence of a new perspective on protein folding, a problem that needs to be conceived as an ‘analytic whole’, will enable us to shed light on the origin of mutational epistasis at the simplest level—within proteins—while also uncovering the reasons why the genetic background in which they occur, a key component of molecular evolution, could foster changes in epistasis effects. Additionally, because mutations are the source of epistasis, more research is needed to determine the impact of post-translational modifications, which can potentially increase the proteome’s diversity by several orders of magnitude, on mutational epistasis and protein evolvability. Finally, a protein evolution thermodynamic-based analysis that does not consider specific mutational steps or epistasis effects will be briefly discussed. Our study explores the complex processes behind the evolution of proteins upon mutations, clearing up some previously unresolved issues, and providing direction for further research.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"473 - 480"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01725-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492569","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

Time-dependent simulation of blood flow through an abdominal aorta with iliac arteries 随时间变化的腹主动脉与髂动脉血流模拟。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-10-18 DOI: 10.1007/s00249-024-01724-w

Grzegorz Górski, Krzysztof Kucab

{"title":"Time-dependent simulation of blood flow through an abdominal aorta with iliac arteries","authors":"Grzegorz Górski, Krzysztof Kucab","doi":"10.1007/s00249-024-01724-w","DOIUrl":"10.1007/s00249-024-01724-w","url":null,"abstract":"<div><p>Atherosclerosis is one of the important diseases of the circulatory system because atherosclerotic plaques cause significant disruption of blood flow. Therefore, it is very important to properly understand these processes and skillfully simulate blood flow. In our work, we consider blood flow through an abdominal aorta with iliac arteries, assuming that the right iliac artery is narrowed by an atherosclerotic lesion. Blood flow is simulated using the laminar, standard <span>(k-omega)</span> and standard <span>(k-epsilon)</span> models. The obtained results show that despite the use of identical initial conditions, the distribution of velocity flow and wall shear stress depends on the choice of flow simulation model. For the <span>(k-epsilon)</span> model, we obtain higher values of speed and wall shear stress on atherosclerotic plaque than in the other two models. The laminar and <span>(k-omega)</span> models predict larger areas where reverse blood flow occurs in the area behind the atherosclerotic lesion. This effect is associated with negative wall shear stress. These two models give very similar results. The results obtained by us, and those reported in the literature, indicate that <span>(k-omega)</span> model is the most suitable for blood flow analysis.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"429 - 445"},"PeriodicalIF":2.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01724-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455353","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

Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution 水溶液中小溶质二聚化过程中的极端焓熵补偿。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-10-15 DOI: 10.1007/s00249-024-01722-y

David J. Scott, Donald J. Winzor

{"title":"Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution","authors":"David J. Scott, Donald J. Winzor","doi":"10.1007/s00249-024-01722-y","DOIUrl":"10.1007/s00249-024-01722-y","url":null,"abstract":"<div><p>This communication summarizes findings from the earliest encounters with extreme enthalpy‒entropy compensation, a phenomenon first detected in the 1950s by a reappraisal of isopiestic and calorimetric measurements on aqueous urea solutions in terms of solute self-association. Because concurrent studies of carboxylic acid association were confined to measurement of the equilibrium constant by conductance, IR spectrophotometry or potentiometric titration measurements, temperature-independence of the dimerization constant was mistakenly taken to signify a value of zero for Δ<span>(H^o)</span> instead of (Δ<span>(H^o)</span> ‒ TΔ<span>(S^o)</span>). In those studies of small-solute self-association the extreme enthalpy‒entropy compensation was reflecting the action of water as a reactant whose hydroxyl groups were competing for the solute carbonyl involved in self-association. Such action gives rise to a positive temperature dependence of Δ<span>(H^o)</span> that could well be operating in concert with that responsible for the commonly observed negative dependence for protein‒ligand interactions exhibiting extreme enthalpy‒entropy compensation, where the solvent contribution to the energetics reflects changes in the extent of ordered water structure in hydrophobic environments.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"373 - 384"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01722-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455352","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

Application of artificial neural network for the mechano-bactericidal effect of bioinspired nanopatterned surfaces 应用人工神经网络研究生物启发纳米图案表面的机械杀菌效果。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-10-07 DOI: 10.1007/s00249-024-01723-x

Ecren Uzun Yaylacı

引用次数: 0

Structural investigation, computational analysis, and theoretical cryoprotectant approach of antifreeze protein type IV mutants 抗冻蛋白 IV 型突变体的结构研究、计算分析和理论低温保护方法。

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-09-27 DOI: 10.1007/s00249-024-01719-7

Azadeh Eskandari, Thean Chor Leow, Mohd Basyaruddin Abdul Rahman, Siti Nurbaya Oslan

{"title":"Structural investigation, computational analysis, and theoretical cryoprotectant approach of antifreeze protein type IV mutants","authors":"Azadeh Eskandari, Thean Chor Leow, Mohd Basyaruddin Abdul Rahman, Siti Nurbaya Oslan","doi":"10.1007/s00249-024-01719-7","DOIUrl":"10.1007/s00249-024-01719-7","url":null,"abstract":"<div><p>Antifreeze proteins (AFPs) have unique features to sustain life in sub-zero environments due to ice recrystallization inhibition (IRI) and thermal hysteresis (TH). AFPs are in demand as agents in cryopreservation, but some antifreeze proteins have low levels of activity. This research aims to improve the cryopreservation activity of an AFPIV. In this in silico study, the helical peptide afp1m from an Antarctic yeast AFP was modeled into a sculpin AFPIV, to replace each of its four <i>α</i>-helices in turn, using various computational tools. Additionally, a new linker between the first two helices of AFPIV was designed, based on a flounder AFPI, to boost the ice interaction activity of the mutants. Bioinformatics tools such as ExPASy Prot-Param, Pep-Wheel, SOPMA, GOR IV, Swiss-Model, Phyre2, MODFOLD, MolPropity, and ProQ were used to validate and analyze the structural and functional properties of the model proteins. Furthermore, to evaluate the AFP/ice interaction, molecular dynamics (MD) simulations were executed for 20, 100, and 500 ns at various temperatures using GROMACS software. The primary, secondary, and 3D modeling analysis showed the best model for a redesigned antifreeze protein (AFP1mb, with afp1m in place of the fourth AFPIV helix) with a QMEAN (Swiss-Model) Z score value of 0.36, a confidence of 99.5%, a coverage score of 22%, and a p value of 0.01. The results of the MD simulations illustrated that AFP1mb had more rigidity and better ice interactions as a potential cryoprotectant than the other models; it also displayed enhanced activity in limiting ice growth at different temperatures.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"385 - 403"},"PeriodicalIF":2.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Computational study on the impact of linkage sequence on the structure and dynamics of lignin 连接序列对木质素结构和动力学影响的计算研究

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-09-19 DOI: 10.1007/s00249-024-01720-0

Derya Vural

{"title":"Computational study on the impact of linkage sequence on the structure and dynamics of lignin","authors":"Derya Vural","doi":"10.1007/s00249-024-01720-0","DOIUrl":"10.1007/s00249-024-01720-0","url":null,"abstract":"<div><p>Lignin, one of the most abundant biopolymers on Earth, is of great research interest due to its industrial applications including biofuel production and materials science. The structural composition of lignin plays an important role in shaping its properties and functionalities. Notably, lignin exhibits substantial compositional diversity, which varies not only between different plant species but even within the same plant. Currently, it is unclear to what extent this compositional diversity plays on the overall structure and dynamics of lignin. To address this question, this paper reports on the development of two models of lignin containing all guaiacyl (G) subunits with varied linkage sequences and makes use of all-atom molecular dynamics simulations to examine the impact of linkage sequence alone on the lignin’s structure and dynamics. This work demonstrates that the structure of the lignin polymer depends on its linkage sequence at temperatures above and below the glass transition temperature (<span>(T_textrm{g})</span>), but the polymers exhibit similar structural properties as it is approaching the viscous flow state (480 K). At low temperatures, both of lignin models have a local dynamics confined in a cage, but the size of cages varies depending on structural differences. Interestingly, at temperatures higher than <span>(T_textrm{g})</span>, the different linkage sequence leads to the subtle dynamical difference which diminishes at 480 K.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"405 - 414"},"PeriodicalIF":2.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Physical aspects of epithelial cell–cell interactions: hidden system complexities 上皮细胞-细胞相互作用的物理方面：隐藏的系统复杂性

IF 2.2 4区生物学

European Biophysics Journal Pub Date : 2024-09-10 DOI: 10.1007/s00249-024-01721-z

Ivana Pajic-Lijakovic, Milan Milivojevic, Peter V. E. McClintock

{"title":"Physical aspects of epithelial cell–cell interactions: hidden system complexities","authors":"Ivana Pajic-Lijakovic, Milan Milivojevic, Peter V. E. McClintock","doi":"10.1007/s00249-024-01721-z","DOIUrl":"10.1007/s00249-024-01721-z","url":null,"abstract":"<div><p>The maintenance of homeostasis and the retention of ordered epithelial cell self-organization are essential for morphogenesis, wound healing, and the spread of cancer across the epithelium. However, cell–cell interactions in an overcrowded environment introduce a diversity of complications. Such interactions arise from an interplay between the cell compressive and shear stress components that accompany increased cell packing density. They can lead to various kinds of cell rearrangement such as: the epithelial-to-mesenchymal cell state transition; live cell extrusion; and cell jamming. All of these scenarios of cell rearrangement under mechanical stress relate to changes in the strengths of the cell–cell and cell–matrix adhesion contacts. The objective of this review study is twofold: first, to provide a comprehensive summary of the biological and physical factors influencing the effects of cell mechanical stress on cell–cell interactions, and the consequences of these interactions for the status of cell–cell and cell–matrix adhesion contacts; and secondly, to offer a bio-physical/mathematical analysis of the aforementioned biological aspects. By presenting these two approaches in conjunction, we seek to highlight the intricate nature of biological systems, which manifests in the form of complex bio-physical/mathematical equations. Furthermore, the juxtaposition of these apparently disparate approaches underscores the importance of conducting experiments to determine the multitude of parameters that contribute to the development of these intricate bio-physical/mathematical models.</p></div>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":"53 7-8","pages":"355 - 372"},"PeriodicalIF":2.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00249-024-01721-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178239","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