The Journal of Physical Chemistry B最新文献

{"title":"Critical Role of Water beyond the Media to Maintain Protein Stability and Activity in Hydrated Deep Eutectic Solvent.","authors":"Tanmoy Khan, Nilimesh Das, Suman Bhowmik, Kuldeep Singh Negi, Pratik Sen","doi":"10.1021/acs.jpcb.4c07039","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c07039","url":null,"abstract":"<p><p>Hydrated deep eutectic solvents (DESs) are recognized for their potential in biocatalysis due to their tunability, biocompatibility, greenness, and ability to keep protein stable and active. However, the mechanisms governing enzyme stability and activity in DES remain poorly understood. Herein, using bromelain as the model enzyme and acetamide (0.5)/urea(0.3)/sorbitol(0.2) as the model DES, we provide experimental evidence that modulation of associated water plays a key role in dictating protein stability and activity in hydrated DES. Specifically, rigid associated water at higher DES concentrations (beyond 40% v/v) stabilizes bromelain through entropy but destabilizes it through enthalpy. On the other hand, flexible associated water dynamics at lower DES concentrations result in an opposite thermodynamic outcome. Importantly, the bulk water dynamics cannot explain the stability trend, which emphasizes the critical role of water near the protein surface. Strikingly, associated water dynamics also correlates strongly with bromelain's proteolytic activity. An increasing flexibility of the associated water dynamics leads to the enhancement of the activity. This is the first study to experimentally link associated water dynamics to enzyme behavior in hydrated DES, offering insights that could guide future developments in solvent engineering for enzyme catalysis.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Evolution of Retinal Chromophore in Early Intermediates of Inward and Outward Proton-Pumping Rhodopsins.","authors":"Taito Urui, Misao Mizuno, Rei Abe-Yoshizumi, Hideki Kandori, Yasuhisa Mizutani","doi":"10.1021/acs.jpcb.4c04793","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c04793","url":null,"abstract":"<p><p>Proton-pumping rhodopsins, which consist of seven transmembrane helices and have a retinal chromophore bound to a lysine side chain through a Schiff base linkage, offer valuable insights for developing unidirectional ion transporters. Despite identical overall structures and membrane topologies of outward and inward proton-pumping rhodopsins, these proteins transport protons in opposing directions, suggesting a rational mechanism that enables protons to move in different directions within similar protein structures. In the present study, we clarified the chromophore structures in early intermediates of inward and outward proton-pumping rhodopsins. Most importantly, common to both pumps, the hydrogen bond of the Schiff base became stronger in the L intermediate than in the unphotolyzed state. Experimental data on the chromophore structures of the L intermediates and proton-pumping activities indicated that the direction of proton release from the Schiff base during the L-to-M transition is determined not by the structure of the retinal chromophore but by the number of negative charges on the extracellular side of the Schiff base. This is in contrast to the idea that the chromophore configuration is a determinant for the direction of proton uptake. The present study, together with our previous studies, clarifies the determining factors of the transport direction in inward and outward proton-pumping rhodopsins.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cation-Cation, Cation-Anion, and Anion-Anion Translation Diffusion in Ionic Liquids─Insight from NMR Relaxometry.","authors":"Elżbieta Masiewicz, Roksana Markiewicz, Rajendra Kumar Singh, Sujeet Kumar Chaurasia, Danuta Kruk","doi":"10.1021/acs.jpcb.4c05069","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c05069","url":null,"abstract":"<p><p>¹H and ¹⁹F spin-lattice relaxation experiments have been performed for a series of ionic liquids: [HMIM][TFSI], [OMIM][TFSI], and [DMIM][TFSI] including the same anion and cations with progressively longer alkyl chains. The experiments were performed in a wide frequency range from 10 kHz to 10 MHz (referring to the ¹H resonance frequency) versus temperature. This extensive data set has been analyzed in terms of a theoretical model including all relevant homonuclear (¹H-¹H and ¹⁹F-¹⁹F) and heteronuclear (¹H-¹⁹F) relaxation pathways and linking the relaxation features to the relative translational diffusion between the ion pairs (cation-cation, cation-anion, and anion-anion). In addition to the comprehensive theoretical approach, closed-form expressions have been provided and applied to determine the diffusion coefficients from the slopes of the linear dependences of the relaxation rates on the square root of the resonance frequency. The combined experimental and theoretical studies have led to the determination of the complete set of diffusion coefficients, forming a consistent picture of the dynamical scenario. In addition to revealing the dynamical properties of the liquids and the influence of the subtle changes in the cation structure on the movement of both cations and anions, the theoretical means for exploiting Nuclear Magnetic Resonance relaxometry for ionic liquids have been provided.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vapor-Deposited High-Entropy Metallic Glasses.","authors":"Qun Yang, Bo-Yan Wang, Zi-Han Zhao, Hui-Feng Zhao, Qing-Zhou Bu, Jing Li, Peng Yu, Hai-Bin Yu","doi":"10.1021/acs.jpcb.4c04677","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c04677","url":null,"abstract":"<p><p>Physical vapor deposition (PVD) at an appropriate temperature has been shown to produce ultrastable glass by the mechanism of surface accelerated diffusion. Recently, high-entropy materials have been discovered to display slower atomic diffusion due to the multicomponent high-entropy effects. How this delayed atomic motion influences the formation and stability of PVD glass remains elusive. Here, we show that PVD high-entropy metallic glasses exhibit distinct behaviors: while the increase in the glass transition temperature is minimal, there is a significant increase in enthalpy. These findings indicate that a wide range of thermal and kinetic properties can be customized by controlling the entropy in PVD glasses, opening up new opportunities for materials design and processing.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlated Molecular Motion during Release of Residual Stress in Polymer Glassy Films.","authors":"Jinzhou Ju, Bin Cheng, Zhichao Jiang, Jingfa Yang, Jiang Zhao","doi":"10.1021/acs.jpcb.4c05588","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c05588","url":null,"abstract":"<p><p>Correlated molecular motion during the process of residual stress release in polymer glassy films is studied at the single-molecule level. Using poly(<i>n</i>-butyl methacrylate) (PnBMA) and poly(vinyl acetate) (PVAc) as the model polymers, thin films fabricated by spin-casting without thermal annealing were chosen as samples for investigation. Single-molecule fluorescence defocused microscopy was used to track the rotational motion of the fluorescent probes doped inside the polymer films. Under the activation effect of residual stress at experimental temperatures, the rotational motions of individual probes are discovered to be correlated a few degrees below the glass transition temperature (<i>T</i>_g), by analyzing the cross-correlation function of the rotational trajectories of different probes. Detailed investigations into the dependence on residual stress strength, intermolecular distance, probe-polymer interaction, and molecular orientation have been conducted. The results have revealed that the physical mechanism of the motion correlation is the randomization process from the state with preferred molecular orientation and presumably the polymer chain stretching.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoxetine Alters the Biophysics of DPPC and DPPG Bilayers through Phase-Dependent and Electrostatic Interactions.","authors":"Tho H Ho, Khai G Tran, Lam K Huynh, Trang T Nguyen","doi":"10.1021/acs.jpcb.4c04631","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c04631","url":null,"abstract":"<p><p>Lipid membranes can control the permeability of a pharmaceutical drug, whereas the drug can induce changes in the structural and biophysical properties of the membranes. Understanding this interplay of drug-lipid membrane interactions can be of great importance in drug design. Here, we present a molecular dynamics study to provide insights into the interactions between the antidepressant fluoxetine and 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) or 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphoglycerol (DPPG) bilayers. It was found that, due to the electrostatic interaction, the headgroup of the zwitterionic DPPC lipid is more stable than that of the negatively charged DPPG lipid, allowing the gel phase to persist even at the elevated temperature. At 25 °C, fluoxetine cannot penetrate into the gel-phase DPPC bilayer, while the electrostatic interaction between positively charged fluoxetine and negatively charged DPPG bilayer retains the drug within the lipid headgroup domain. When the temperature is increased to 45 °C, both neutral and charged forms of fluoxetine can partition into the DPPC and DPPG bilayers spontaneously. Analysis of the biophysical and structural changes in both DPPC and DPPG bilayers in the presence of fluoxetine revealed a phase-dependent effect. The binding of fluoxetine to the lipid bilayers limits the movement and orientation of the drug. These findings shed light on the interactions between a commonly prescribed antidepressant and lipid membranes, and such information can be beneficial to the development of potential therapeutic agents.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating How Lysophosphatidylcholine and Lysophosphatidylethanolamine Enhance the Membrane Permeabilization Efficacy of Host Defense Peptide Piscidin 1.","authors":"Amy Rice, Andriana C Zourou, Evan P Goodell, Riqiang Fu, Richard W Pastor, Myriam L Cotten","doi":"10.1021/acs.jpcb.4c05845","DOIUrl":"10.1021/acs.jpcb.4c05845","url":null,"abstract":"<p><p>Lysophospholipids (LPLs) and host defense peptides (HDPs) are naturally occurring membrane-active agents that disrupt key membrane properties, including the hydrocarbon thickness, intrinsic curvature, and molecular packing. Although the membrane activity of these agents has been widely examined separately, their combined effects are largely unexplored. Here, we use experimental and computational tools to investigate how lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), an LPL of lower positive spontaneous curvature, influence the membrane activity of piscidin 1 (P1), an α-helical HDP from fish. Four membrane systems are probed: 75:25 C16:0-C18:1 PC (POPC)/C16:0-C18:1 phosphoglycerol (POPG), 50:25:25 POPC/POPG/16:0 LPC, 75:25 C16:0-C18:1 PE (POPE)/POPG, and 50:25:25 POPE/POPG/14:0 LPE. Dye leakage, circular dichroism, and NMR experiments demonstrate that while the presence of LPLs alone does not induce leakage-proficient defects, it boosts the permeabilization capability of P1, resulting in an efficacy order of POPC/POPG/16:0 LPC > POPE/POPG/14:0 LPE > POPC/POPG > POPE/POPG. This enhancement occurs without altering the membrane affinity and conformation of P1. Molecular dynamics simulations feature two types of asymmetric membranes to represent the imbalanced (\"area stressed\") and balanced (\"area relaxed\") distribution of lipids and peptides in the two leaflets. The simulations capture the membrane thinning effects of P1, LPC, and LPE, and the positive curvature strain imposed by both LPLs is reflected in the lateral pressure profiles. They also reveal a higher number of membrane defects for the P1/LPC than P1/LPE combination, congruent with the permeabilization experiments. Altogether, these results show that P1 and LPLs disrupt membranes in a concerted fashion, with LPC, the more disruptive LPL, boosting the permeabilization of P1 more than LPE. This mechanistic knowledge is relevant to understanding biological processes where multiple membrane-active agents such as HDPs and LPLs are involved.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Site Red-Edge Excitation Shift Reveals the Residue-Specific Solvation Dynamics during the Native to Amyloid-like Transition of an Amyloidogenic Protein.","authors":"Sonal R More, Santosh Kumar Jha","doi":"10.1021/acs.jpcb.4c07067","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c07067","url":null,"abstract":"<p><p>Changes in water-protein interactions are crucial for proteins to achieve functional and nonfunctional conformations during structural transitions by modulating local stability. Amyloid-like protein aggregates in deteriorating neurons are hallmarks of neurodegenerative disorders. These aggregates form through significant structural changes, transitioning from functional native conformations to supramolecular cross-β-sheet structures via misfolded and oligomeric intermediates in a multistep process. However, the site-specific dynamics of water molecules from the native to misfolded conformations and further to oligomeric and compact amyloid structures remain poorly understood. In this study, we used the fluorescence method known as red-edge excitation shift (REES) to investigate the solvation dynamics at specific sites in various equilibrium conformations en route to the misfolding and aggregation of the functional domain of the TDP-43 protein (TDP-43^tRRM). We generated three single tryptophan-single cysteine mutants of TDP-43^tRRM, with the cysteines at different positions and tryptophan at a fixed position. Each sole cysteine was fluorescently labeled and used as a site-specific fluorophore along with the single tryptophan, creating four monitorable sites for REES studies. By investigating the site-specific extent of REES, we developed a residue-specific solvation dynamics map of TDP-43^tRRM during its misfolding and aggregation. Our observations revealed that solvation dynamics progressively became more rigid and heterogeneous to varying extents at different sites during the transition from native to amyloid-like conformations.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the Dynamics of a Complex, Multipathway Reaction: Insulin Dimer Dissociation.","authors":"Kwanghoon Jeong, Spencer C Guo, Sammy Allaw, Aaron R Dinner","doi":"10.1021/acs.jpcb.4c06933","DOIUrl":"10.1021/acs.jpcb.4c06933","url":null,"abstract":"<p><p>The protein hormone insulin forms a homodimer that must dissociate to bind to its receptor. Understanding the kinetics and mechanism of dissociation is essential for the rational design of therapeutic analogs. In addition to its physiological importance, this dissociation process serves as a paradigm for coupled (un)folding and (un)binding. Based on previous free energy simulations, insulin dissociation is thought to involve multiple pathways with comparable free energy barriers. Here, we analyze the mechanism of insulin dimer dissociation using a recently developed computational framework for estimating kinetic statistics from short-trajectory data. These statistics indicate that the likelihood of dissociation (the committor) closely tracks the decrease in the number of (native and nonnative) intermonomer contacts and the increase in the number of water contacts at the dimer interface; the transition state with equal likelihood of association and dissociation corresponds to an encounter complex with relatively few native contacts and many nonnative contacts. We identify four pathways out of the dimer state and quantify their contributions to the rate as well as their exchange by computing reactive fluxes. We show that both the pathways and their extents of exchange can be understood in terms of rotations around three axes of the dimer structure. Our results provide insights into the kinetics of insulin analogs and, more generally, how to characterize complex, multipathway processes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solvation Dynamics and Microheterogeneity in Deep Eutectic Solvents.","authors":"Srijan Chatterjee, Tubai Chowdhury, Sayan Bagchi","doi":"10.1021/acs.jpcb.4c06295","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06295","url":null,"abstract":"<p><p>Deep eutectic solvents have attracted considerable attention due to their unique properties and their potential to replace conventional solvents in diverse applications, such as catalysis, energy storage, and green chemistry. However, despite their broad use, the microscopic mechanisms governing solvation dynamics and the role of hydrogen bonding in deep eutectic solvents remain insufficiently understood. In this article, we present our contributions toward unravelling the micro heterogeneity within deep eutectic solvents by combining vibrational Stark spectroscopy and two-dimensional infrared spectroscopy with molecular dynamics simulations. Our findings demonstrate how the composition, constituents, and addition of water significantly influence the heterogeneous hydrogen bonding network and solvent dynamics within these systems. These insights provide valuable guidance for the design of next-generation solvents tailored to specific applications. By integrating experimental and computational approaches, this work sheds light on the intricate relationship between solvation dynamics and nanostructure in deep eutectic solvents, ultimately paving the way for innovative advances in solvent design.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}