The Journal of Physical Chemistry B最新文献

{"title":"Tables Turned─Structural Mechanisms of Target-Induced miRNA Destabilization.","authors":"Ukesh Karki, Prem Chapagain","doi":"10.1021/acs.jpcb.5c01093","DOIUrl":"10.1021/acs.jpcb.5c01093","url":null,"abstract":"<p><p>Argonaute 2 (Ago2) loaded with a microRNA (miRNA) forms an RNA-induced silencing complex (RISC), which targets mRNA through miRNA-mRNA base pairing, leading to translation inhibition or degradation of the target mRNA. However, certain target mRNAs can turn the table by binding to the miRNA-Ago complex with high complementarity, resulting in the destruction of the miRNA itself, and the process is commonly known as target-directed miRNA degradation (TDMD). Highly complementary targets can also promote miRNA destabilization and release from Ago2. However, the dynamic nature of the target-induced effects of miRNA-Ago2 interactions and miRNA dissociation from Ago2 is not well understood. The lack of a complete crystal structure of the complex involved in TDMD has limited computational study of the dynamics of target or miRNA destabilization. In this work, we utilized AlphaFold 3 (AF3) to model the full structures of Ago2-miR-27a-mRNA-target complexes and investigated the dynamics of miRNA-mRNA and miRNA-Ago2 interactions using molecular dynamics simulations. We chose miR-27a because it has not only been extensively investigated for its involvement in cancer biology but it is also a known target for its degradation via TDMD by viral mRNAs such as HVS HSUR1 from Herpesvirus saimiri. We systematically changed the targets from seed-only base pairing (target ATF3) to seed and extensive supplementary base pairing (target HVS HSUR1) to compare the stability of the miRNA-Ago2 complexes. We find that the sequence complementarity in seed, central, and supplementary pairings as well as the structural agility of Ago2 allow for differential stability of miRNA binding, potentially facilitating dissociation under different conditions.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5166-5175"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953379","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":"On the Possibility of Chiral Symmetry Breaking in Liquid Hydrogen Peroxide.","authors":"Roberto Menta, Pablo G Debenedetti, Roberto Car, Pablo M Piaggi","doi":"10.1021/acs.jpcb.5c01780","DOIUrl":"10.1021/acs.jpcb.5c01780","url":null,"abstract":"<p><p>Molecular chirality is a key concept in chemistry with implications for the origin of life and the manufacturing of pharmaceuticals. Previous simulations of a chiral molecular model with an energetic bias toward homochiral interactions show a spontaneous symmetry-breaking transition from a supercritical racemic liquid into a subcritical liquid enriched in one of the two enantiomers. Here, we employ molecular dynamics simulations in order to test the possible existence of this phenomenon in hydrogen peroxide, the smallest chiral molecule. For this purpose, we study the fluid phase of this substance between 100 and 1500 K, and from 100 kPa to 1 GPa. We find a glass transition and we suggest that hydrogen bonds play a central role in such behavior. We also test the possibility of observing chiral symmetry breaking by performing both constant temperature and cooling simulations at multiple pressures, and we do not observe the phenomenon. An analysis of the structure of the liquid shows negligible differences between homochiral and heterochiral interactions, supporting the difficulty in observing chiral symmetry breaking. If hydrogen peroxide manifests spontaneous chiral symmetry breaking, it likely takes place significantly below room temperature and is hidden by other phenomena, such as the glass transition or crystallization. More broadly, our results, and recent experimental observations, suggest that greater molecular complexity is needed for spontaneous chiral symmetry breaking in the liquid phase to occur.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5335-5342"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092090","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":"Orientations of Water Molecules near Globular Protein and Lipid Membrane.","authors":"Vladimir P Voloshin","doi":"10.1021/acs.jpcb.5c00775","DOIUrl":"10.1021/acs.jpcb.5c00775","url":null,"abstract":"<p><p>In computer models of aqueous solutions of globular protein and lipid bilayer membrane, the orientations of water molecules relative to the directions to organic surfaces at different distances were studied. Distributions of distances between molecular surfaces and angles between the internal vectors of water molecules (dipole moment, normal vector, HH-vector) and these directions to organics allowed us to identify molecular layers with fundamentally different orientations. The most probable orientations of the molecules in the nearest layers have been determined and described in detail. It is shown that water molecules in the first layer around the protein most often adopt an orientation that allows them to form donor and acceptor hydrogen bonds with the surface atoms of the protein. Near the membrane, molecules with donor orientations are also most abundant, while acceptor orientations are absent. Instead, orientations describing the interaction of water molecules with hydrophobic regions of the lipid surface are present. Moving to the second and subsequent layers each time radically changes the distribution of orientations, but in all layers except the first, the orientations around the protein and membrane do not differ. The presented method of analysis is not exclusively for water molecules and can be used to study the orientations of any rigid molecules.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5224-5233"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074945","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":"The Correlated States Theory of the Hydrophobic Effect.","authors":"Maxim P Evstigneev, Alexei D Degtyar, Anastasia Olegovna Lantushenko","doi":"10.1021/acs.jpcb.5c01214","DOIUrl":"10.1021/acs.jpcb.5c01214","url":null,"abstract":"<p><p>Starting from Frank and Evans' \"iceberg\" model of hydrophobic hydration of small molecules (the \"microscopic\" hydrophobic effect, HE) published in 1945, much has been done with respect to understanding the nature of HE and elaborating a quantitative theory able to describe the thermodynamic profile (the \"signature\" of HE) for the large volume of experimental data accumulated to date. Generally, three sets of approaches addressing this issue were suggested, ranging from the approval of the central role of the water shell to the complete denial of its role, with the focus placed on the solute and its interactions with surrounding water. For this reason, some controversy is still present in understanding the fundamental nature of HE, even at the \"microscopic\" scale. Nevertheless, the general tendency of the past decade seems to have shifted toward a greater role of the water environment in determining the thermodynamic profile of HE, with a designated place for solute-water interactions as a fine-tuning of thermodynamic observables. In the present work, we developed a novel view on HE at the microscopic scale, appearing as a consequence of solute-water correlated translational and orientational vibration motion, emerging as a new property of hydrophobic hydration/solvation (the Correlated States Theory of HE). We built a fully analytical description of this process, which has enabled us to quantify the \"signature\" of HE for extended thermodynamic data sets without employing molecular simulations or any numerical functions in the core of the theory. As a consequence, our approach provides a self-consistent view on the known major experimental manifestations of HE across an extended temperature range, addresses some controversial issues existing to date, and creates a new augmentation to current knowledge. Most importantly, the suggested approach offers a paradigm shift from the currently dominating views on HE as a consequence of water-water interactions and the \"excluded volume effect\" toward the central role of solute-water interactions, and provides the first nonempirical proof of the validity of SASA-based computational models of hydrophobic hydration/solvation, which have been utilized on an empirical basis for more than 40 years.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5245-5267"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074947","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":"Hydrophobic Interactions in Aqueous Osmolyte Solutions: Thermodynamics of Solvation and Implication on Protein Stability.","authors":"Cedrix J Dongmo Foumthuim","doi":"10.1021/acs.jpcb.5c00785","DOIUrl":"10.1021/acs.jpcb.5c00785","url":null,"abstract":"<p><p>The effect of cosolvents urea and trimethylamine-<i>N</i>-oxide (TMAO) on hydrophobic association mechanisms is investigated by employing molecular dynamics simulations and free energy calculations. Three nonpolar moieties are used to model the hydrophobic interactions: <i>n</i>-hexane <i>n</i>C₆H₁₄, neopentane C₅H₁₂, and cyclohexane cC₆H₁₂. These hydrophobic model systems are subsequently immersed in four different solvent models with varied composition: pure water, aqueous urea, aqueous TMAO, and mixed urea-TMAO ternary solution. The solute-solute potentials of mean force (PMF), solute-water, and solute-cosolvent distribution functions are reported. Both urea and TMAO are found to have only moderate effects on hydrophobic associations, thereby mainly acting as glue bridging between pairwise hydrophobic moieties holding them together. Furthermore, it is seen that TMAO mediates the formation of hydrogen bonds between its oxygen atom and water or urea while still favoring the hydrophobic contacts with the hydrophobic surface, thereby acting as a kind of amphiphile displacing water or urea from the inner solvation shell of the hydrophobic solutes investigated here to the bulk. The analyses of the enthalpic and entropic contributions to PMFs indicate that configurations at the contact minimum are both enthalpically and entropically favorable, though, with a large entropic contribution, whereas solute-separated minimum configurations are dominantly enthalpically driven, induced by stabilizing water hydrogen bonding. To provide a more factual and general perspective to the simplistic hydrophobic models, simulations are also performed on a realistic-like hydrophobic model, β2-microglobulin (β2m), a paradigmatic protein model for amyloid studies. Results show that TMAO protects the β2m folded state by its strong preferential exclusion from the close vicinity of its surface. Contrariwise, urea moieties likely accumulate at the protein surface, thereby displacing water molecules from the hydration shell to the bulk, thus promoting an unfolded state of the protein.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5150-5165"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construing the Interaction of Antioxidant Coumarin Derivative Daphnetin with Double-Stranded Calf Thymus Deoxyribonucleic Acid: Insights into the Binding Mechanism and Effects on Oxidative DNA Damage.","authors":"Sana Quraishi, Sibasree Hojaisa, Kalpana Kumari, Erica W M Marboh, Kripamoy Aguan, Anupam Nath Jha, Atanu Singha Roy","doi":"10.1021/acs.jpcb.4c08734","DOIUrl":"10.1021/acs.jpcb.4c08734","url":null,"abstract":"<p><p>Oxidative damage to DNA has significant consequences for human health and is identified as one of the key contributors to the onset and advancement of several diseases. Therefore, it is crucial to prevent oxidatively driven DNA lesions in both humans and other organisms. This study investigated the potential of daphnetin to protect DNA from oxidative damage and its binding interaction with calf thymus DNA (ct-DNA) employing multispectroscopic techniques, viscosity measurements, gel electrophoresis, docking studies, and molecular dynamics (MD) simulation. The 2-thiobarbituric acid (TBA) colorimetry assay and agarose gel electrophoresis demonstrated that daphnetin acted to protect the deoxyribose sugar and the backbone of the double-stranded DNA structure from damage caused by hydroxyl radicals. Moreover, various <i>in vitro</i> antioxidant assays (DPPH·,·OH, and <math><msup><msub><mi>O</mi><mn>2</mn></msub><mrow><mo>·</mo><mo>-</mo></mrow></msup></math>) revealed scavenging activity comparable to that of the antioxidant ascorbic acid, providing insight into the mechanism of DNA protection. UV-vis, fluorescence studies confirmed the complex formation between ct-DNA and daphnetin, with a binding constant on the order of 10³ M^-1, suggesting a weak binding affinity. Competitive displacement assay, thermal denaturation studies, and viscosity measurements indicated groove binding, further supported by molecular docking studies. Furthermore, MD simulation studies confirmed a stable binding of daphnetin with DNA without compromising the structural integrity of DNA.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5119-5135"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074939","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":"Perfluorooctanoic Acid Destabilizes Hemoglobin Structure at Submicromolar Concentrations.","authors":"Rhys C Trousdale, Monika Tokmina-Lukaszewska, Brian Bothner, Robert A Walker","doi":"10.1021/acs.jpcb.5c01380","DOIUrl":"10.1021/acs.jpcb.5c01380","url":null,"abstract":"<p><p>Perfluorooctanoic acid's (PFOA) effects on human hemoglobin (Hb) at micromolar and submicromolar PFOA concentrations were investigated using time-correlated single photon counting (TCSPC) fluorescence, native mass spectrometry (NMS), and ion mobility spectrometry (IMS). TCSPC results show that tryptophan fluorescence quenching mechanisms in Hb change from Förster resonance energy transfer (FRET) with the heme to charge transfer to the peptide backbone as the PFOA concentration increases. NMS showed 4 lower and 2 higher affinity sites for PFOA interacting with Hb. At concentrations as low as 10 nM, 2 PFOA molecules bind to Hb, leading to destabilization of the complex, loss of an α subunit, and release of heme. Together, these data show that PFOA alters the biophysical properties of human Hb in ways that suggest allosteric inhibition.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5217-5223"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074946","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":"Folding Transition of Single Semiflexible Polymers Controlled by the Range of Intermonomer Attractions.","authors":"Jinping Li, Chenyang An, Yongjian Zhu, Tiantian Wan, Bin Zhu, Binzhou Wang, Chuandong Jia, Teng Lu, Liang Dai, Tao Chen","doi":"10.1021/acs.jpcb.5c01916","DOIUrl":"10.1021/acs.jpcb.5c01916","url":null,"abstract":"<p><p>Semiflexible polymer folding has been employed by nature for protein folding and by researchers for designing smart materials and nanomachines. Hence, it is of great importance to understand and control semiflexible polymer folding. Here, we find that the range of intermonomer attraction, or the width of attraction (<i>w</i>), can significantly control the structural phase diagram of a semiflexible polymer through entropic effects. As <i>w</i> decreases, the extent of entropy loss depends on the specific folded structures, reshaping the energy landscape and resulting in a change in the folding mechanism. Furthermore, a reduced width of attraction can facilitate specific interactions and the formation of particular structures, which may further enhance folding and binding capabilities of some biomacromolecules. For the coil-globule transition of stiff chains, the critical temperature approximately follows <i>k</i>_B<i>T</i>*/ε ∼ <i>w</i>^1/3, and the entropic loss is approximately described by Δ<i>S</i>/<i>k</i>_B ∼ <i>w</i>^-1/3. Notably, this effective exponent of 1/3 differs from the scaling exponent of 2/3 derived from Odijk's theory. To better understand the underlying mechanisms contributing to this discrepancy, we mapped the polymer folding problem to an adsorption problem. Our findings suggest that the deviation from Odijk scaling is likely due to differences in the shapes of the attractive potentials.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5343-5353"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951603","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":"Effect of Flow on Charge Transport in Semidilute Redox-Active Polymer Solutions.","authors":"Dejuante W Walker, Charles D Young, Charles E Sing","doi":"10.1021/acs.jpcb.5c01425","DOIUrl":"10.1021/acs.jpcb.5c01425","url":null,"abstract":"<p><p>Redox-active polymers (RAPs) are polyelectrolytes that can undergo redox self-exchange reactions and can thus store charge. This ability makes them of interest as an electrolyte material in redox flow batteries due to their molecular size, chemical modularity, and ability to quickly charge and discharge. It is therefore important to understand how charge is transported at the molecular level, under different conditions such as RAP concentration, flow type, and flow strength. While previous efforts have explored these mechanisms in detail, they have primarily focused on charge transport dynamics in equilibrium <i>or</i> in dilute nonequilibrium situations. In this work, we seek to build upon these previous models by accounting for <i>both</i> nonequilibrium dynamics into semidilute RAP solutions and showing ways in which intermolecular interactions couple to strong flows to affect charge transport. Using recent advances in modeling multichain systems in flow, we show that for a single charge, both extensional and shear flow promote charge transport by extending the polymer conformation. This allows the charge to hop along a longer path along the same chain while also increasing the number of chain-chain collisions needed for interchain hopping. We also show that, when multiple charges are present in equilibrium, the charge transport decreases monotonically at all polymer concentrations but decreases the most below the overlap concentration. We attribute this to a decreased probability of chain-to-chain collisions, leading to a concomitant decrease in charge hopping with increasing charge fraction. Overall, we show how charge fraction, concentration, and flow strength couple to produce enhanced charge transport in concentrated solutions in both extensional and shear flows at semidilute concentrations.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"5322-5334"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074940","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":"GROMOS-RONS: A Force Field for Simulations of Reactive Oxygen and Nitrogen Species.","authors":"Rodrigo M Cordeiro","doi":"10.1021/acs.jpcb.5c01926","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c01926","url":null,"abstract":"<p><p>Reactive oxygen and nitrogen species (RONS) play pivotal roles in biological and atmospheric systems, yet their transient nature challenges experimental study. Molecular dynamics (MD) simulations offer a powerful alternative, as long as reliable molecular mechanical models are available that accurately reproduce key physical properties of the simulated species. Correct partitioning behavior is crucial for biomolecular and atmospheric chemistry simulations, where RONS interactions at interfaces─such as phospholipid membranes and water-air boundaries─underpin essential processes. This study presents GROMOS-RONS, a force field for MD simulations of RONS and related compounds within the framework of the GROMOS 53A6 and 54A7 force field families. By integrating electronic structure calculations, thermodynamic integration, and equilibrium MD simulations, parameters were optimized to reproduce solvation free energies of various RONS in both water and hydrophobic media. In the case of ionic species, emphasis was placed on the correct hydration structure and ion-pairing tendencies. This force field provides a robust, validated tool for studying RONS dynamics and interactions across diverse scientific domains.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172039","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}