The Journal of Physical Chemistry B最新文献

{"title":"IDP-Bert: Predicting Properties of Intrinsically Disordered Proteins Using Large Language Models.","authors":"Parisa Mollaei, Danush Sadasivam, Chakradhar Guntuboina, Amir Barati Farimani","doi":"10.1021/acs.jpcb.4c02507","DOIUrl":"10.1021/acs.jpcb.4c02507","url":null,"abstract":"<p><p>Intrinsically disordered Proteins (IDPs) constitute a large and structureless class of proteins with significant functions. The existence of IDPs challenges the conventional notion that the biological functions of proteins rely on their three-dimensional structures. Despite lacking well-defined spatial arrangements, they exhibit diverse biological functions, influencing cellular processes and shedding light on disease mechanisms. However, it is expensive to run experiments or simulations to characterize this class of proteins. Consequently, we designed an ML model that relies solely on amino acid sequences. In this study, we introduce the IDP-Bert model, a deep-learning architecture leveraging Transformers and Protein Language Models to map sequences directly to IDP properties. Our experiments demonstrate accurate predictions of IDP properties, including Radius of Gyration, end-to-end Decorrelation Time, and Heat Capacity.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12030-12037"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714882","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":"Marangoni-Induced Honeycomb Structures in Spin-Coated Polymer Nanocomposite Films.","authors":"Aria C Zhang, Kohji Ohno, Russell J Composto","doi":"10.1021/acs.jpcb.4c06630","DOIUrl":"10.1021/acs.jpcb.4c06630","url":null,"abstract":"<p><p>This study investigates Marangoni effect-induced structural changes in spin-coated polymer nanocomposite (PNC) films composed of poly(methyl methacrylate)-grafted silica nanoparticles (NPs) and poly(styrene-<i>ran</i>-acrylonitrile). Films cast from methyl isobutyl ketone (MIBK) solvent exhibit distinct hexagonal honeycomb cells with thickness gradients driven by surface tension variations. Atomic force microscopy reveals protruded ridges and junctions at cell intersections, where NP concentration is the highest. Upon annealing at 155 °C, NPs segregate to the surface due to their lower surface energy, and the initially protruding features flatten and eventually form depressed channels while maintaining higher NP density than surrounding areas. Time-of-flight secondary ion mass spectrometry corroborated these findings, highlighting enhanced surface segregation of NPs in MIBK films. These defects can be eliminated using methyl isoamyl ketone (MIAK) as a solvent that produces homogeneous films of uniform thickness. This study highlights the impact of the Marangoni effect on the microstructure and surface properties of PNC films, providing insights for enhancing film quality and performance.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12268-12278"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737819","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 Influence of Ionic Environment on Nucleosome-Mica Interactions Revealed via Molecular Dynamics Simulations.","authors":"Nilusha L Kariyawasam, Jeff Wereszczynski","doi":"10.1021/acs.jpcb.4c04223","DOIUrl":"10.1021/acs.jpcb.4c04223","url":null,"abstract":"<p><p>Nucleosomes are the fundamental units of DNA compaction, playing a key role in modulating gene expression. As such, they are widely studied through both experimental and computational methods. While atomic force microscopy (AFM) is a powerful tool for visualizing and characterizing both canonical and modified nucleosomes, it relies on nucleosome interactions with mica surfaces. These interactions occur through cations adsorbed on the negatively charged mica, but the specific influences of monovalent and divalent cations on nucleosome adsorption remain unclear. In this study, we used molecular dynamics simulations to investigate how monovalent potassium ions and divalent magnesium ions affect nucleosome binding to mica surfaces. We also explored the impact of pretreated mica surfaces on nucleosome binding and structure. Our findings reveal that nucleosome-mica interactions depend on the type of cations present, which leads to distinct effects on nucleosome structure. Notably, nucleosomes bind effectively to mica surfaces in the presence of potassium ions with minimal structural perturbations.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12038-12049"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737824","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":"Rationalize the Functional Roles of Protein-Protein Interactions in Targeted Protein Degradation by Kinetic Monte Carlo Simulations.","authors":"Zhaoqian Su, Shanye Yin, Yinghao Wu","doi":"10.1021/acs.jpcb.4c06497","DOIUrl":"10.1021/acs.jpcb.4c06497","url":null,"abstract":"<p><p>Targeted protein degradation is a promising therapeutic strategy to tackle disease-causing proteins that lack binding pockets for traditional small-molecule inhibitors. Its first step is to trigger the proximity between a ubiquitin ligase complex and a target protein through a heterobifunctional molecule, such as proteolysis targeting chimeras (PROTACs), leading to the formation of a ternary complex. The properties of protein-protein interactions play an important regulatory role during this process, which can be reflected by binding cooperativity. Unfortunately, although computer-aided drug design has become a cornerstone of modern drug development, the endeavor to model-targeted protein degradation is still in its infancy. The development of computational tools to understand the impacts of protein-protein interactions on targeted protein degradation, therefore, is highly demanded. To reach this goal, we constructed a nonredundant structural benchmark of the most updated ternary complexes and applied a kinetic Monte Carlo method to simulate the association between ligases and PROTAC-targeted proteins in the benchmark. Our results show that proteins in most complexes with positive cooperativity tend to associate into native-like configurations more often. In contrast, proteins very likely failed to associate into native-like configurations in complexes with negative cooperativity. Moreover, we compared protein-protein association through different interfaces generated from molecular docking. The native-like binding interface shows a higher association probability than all the other alternative interfaces only in the complex with positive cooperativity. These observations support the idea that the formation of ternary complexes is closely regulated by the binary interactions between proteins. Finally, we applied our method to cyclin-dependent kinases 4 and 6 (CDK4/6). We found that their interactions with the ligase are not as similar as their structures. Altogether, our study paves the way for understanding the role of protein-protein interactions in the PROTAC-induced ternary complex formation. It can potentially help in searching for degraders that selectively target specific proteins.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12092-12100"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749405","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":"Editorial Guidelines for Computational Studies of Ligand Binding Using MM/PBSA and MM/GBSA Approximations Wisely.","authors":"Benoît Roux, Christophe Chipot","doi":"10.1021/acs.jpcb.4c06614","DOIUrl":"10.1021/acs.jpcb.4c06614","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12027-12029"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764495","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 Confinement on the Translational Diffusivity of Small Dye Molecules in Thin Polystyrene Films and Its Connection to <i>T</i>_g-Confinement and Fragility-Confinement Effects.","authors":"Tian Lan, Tong Wei, Logan M Fenimore, John M Torkelson","doi":"10.1021/acs.jpcb.4c06495","DOIUrl":"10.1021/acs.jpcb.4c06495","url":null,"abstract":"<p><p>Using fluorescence, we study the impact of nanoscale confinement on the translational diffusivity (<i>D</i>) of trace levels of a small-molecule dye, 9,10-bis(phenylethynyl)anthracene (BPEA), in supported polystyrene (PS) films via Förster resonance energy transfer (FRET). Reductions in BPEA diffusivity are observed in films thinner than ∼200 nm, with <i>D</i> decreasing by 80-90% in 100 nm-thick films compared to bulk. The activation energy of BPEA diffusivity increases from ∼210 kJ/mol in bulk films to ∼370 kJ/mol in 130 nm-thick films. BPEA exhibits a greater diffusivity-confinement effect than a larger dye, decacyclene, in terms of the length scale at which the effects of confinement become evident and the percentage reduction in diffusivity. For both BPEA and decacyclene, the diffusivity-confinement effect in supported PS films occurs at a length scale much larger than that for the glass transition temperature (<i>T</i>_g)-confinement effect and somewhat larger than that for the fragility-confinement effect. This difference in confinement-effect length scales can be rationalized as follows: small-molecule dye diffusivity relates predominantly to short times in the α-relaxation distribution, whereas <i>T</i>_g relates to long times in the α-relaxation distribution, and fragility reflects the overall breadth of this relaxation time distribution. If confinement results in a narrower relaxation time distribution in PS films with the short-time relaxations being shifted to longer times and the longest-time relaxation regimes being shifted to shorter times, then <i>T</i>_g, diffusivity, and fragility all decrease at sufficient levels of confinement. If the narrowing with confinement begins with the shortest relaxation time regimes, then fragility and small-molecule dye diffusivity are influenced by confinement at larger length scales than <i>T</i>_g.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12259-12267"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764497","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":"Influence of an Imposed Network on One- and Three-Dimensional Photonic Liquid Crystal Structures through the Polymer Template Technique.","authors":"Rajalaxmi Sahoo, Gayathri R Pisharody, D S Shankar Rao, C V Yelamaggad, S Krishna Prasad","doi":"10.1021/acs.jpcb.4c06196","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06196","url":null,"abstract":"<p><p>We describe the first investigations on the influence of an imposed network on the photonic band gap (PBG) structure of the liquid crystal (LC) phase through the polymer template technique. The technique consists of using a cholesteric (Ch) phase as a base for photopolymerizing a difunctional monomer, which is then removed after polymerization, leaving only the polymer scaffold template. The templated structure obtained is utilized to adjust the PBG structure of the filled LC material, exhibiting both a one-dimensional PBG (Ch phase) and a three-dimensional PBG structure (TGBC* phase with smectic C* blocks). Selective reflection measurements indicate that the imprint polymer network of the template impacts the pitch of the Ch and TGBC* phases. The absorption peaks are visible because of two distinct twisted arrangements, one originating from the template and the other from the refilled chiral substance. In the templated cell, the central wavelength (λ_min) of PBG of the refilled sample red-shifts, as well as the width of the PBG gets enhanced compared to that for the sample in the regular (nontemplated) cell. For example, in the TGBC* phase, the λ_min value red-shifts by 369 nm, and the width of the PBG enlarges by 50%. Additionally, the lattice spacing arising due to the periodicity of the SmC* helix in 2-dimension in the TGBC* phase gets enhanced. These findings demonstrate the polymer template method's effectiveness in tuning the mesophase's PBG in all three dimensions.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811535","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":"Interaction between the Polyelectrolytes Unfractionated Heparin and Universal Heparin Reversal Agents.","authors":"Hemant K Saini, A Louise Creagh, Chanel C La, David Thiam En Lim, Jayachandran N Kizhakkedathu, Charles A Haynes, Simcha Srebnik, Suzana K Straus, Matthias Ballauff","doi":"10.1021/acs.jpcb.4c07120","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c07120","url":null,"abstract":"<p><p>The interaction of unfractionated heparin (UFH) with universal heparin reversal agent 7 (UHRA-7) is investigated. UHRA-7 is composed of a hyperbranched polyglycerol core onto which an array of methylated tris(2-aminoethylamine) (Me-TREN) charged groups is grafted, which in turn are shielded with a layer of small chain poly(ethylene glycol) methyl ether (mPEG) chains. This system has previously been shown to be biocompatible and to be effective at neutralizing heparin. The binding constant <i>K</i>_b was determined from isothermal titration calorimetry experiments, at temperatures ranging from 278 to 323 K and salt concentrations ranging from 0.06 to 0.20 M NaCl. The data were analyzed in terms of a number of different theoretical models to determine the contribution of counterion release and water release to driving the interaction between UFH and UHRA-7. With the support of NMR and molecular dynamics simulation data, a model of the interaction between UFH and UHRA-7 is proposed. The binding of heparin and universal heparin reversal agent 7 is mainly due to charge-charge interactions between the negatively charged units on UFH with positively charged Me-TREN and mPEG chains.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811542","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":"Characterizing the Slow Dynamics of the Swap Monte Carlo Algorithm.","authors":"Kumpei Shiraishi, Ludovic Berthier","doi":"10.1021/acs.jpcb.4c06702","DOIUrl":"10.1021/acs.jpcb.4c06702","url":null,"abstract":"<p><p>The swap Monte Carlo algorithm introduces nonphysical dynamic rules to accelerate the exploration of the configuration space of supercooled liquids. Its success raises deep questions regarding the nature and physical origin of the slow dynamics of dense liquids and how it is affected by swap moves. We provide a detailed analysis of the slow dynamics generated by the swap Monte Carlo algorithm at very low temperatures in two glass-forming models. We find that the slowing down of the swap dynamics is qualitatively distinct from its local Monte Carlo counterpart, with considerably suppressed dynamic heterogeneity at both single-particle and collective levels. Our results suggest that local kinetic constraints are drastically reduced by swap moves, leading to nearly Gaussian and diffusive dynamics and weakly growing dynamic correlation length scales. The comparison between static and dynamic fluctuations shows that swap Monte Carlo is a nearly optimal local equilibrium algorithm, suggesting that further progress should necessarily involve collective or driven algorithms.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12279-12291"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764545","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":"Classical Models of Hydroxide for Proton Hopping Simulations.","authors":"Ankita Dutta, Themis Lazaridis","doi":"10.1021/acs.jpcb.4c05499","DOIUrl":"10.1021/acs.jpcb.4c05499","url":null,"abstract":"<p><p>Hydronium (H₃O⁺) and hydroxide (OH^-) ions perform structural diffusion in water via sequential proton transfers (\"Grotthuss hopping\"). This phenomenon can be accounted for by interspersing stochastic proton transfer events in classical molecular dynamics simulations. The implementation of OH^--mediated proton hopping is particularly challenging because classical force fields are known to produce overcoordinated solvation structures around the OH^- ion. Here, we first explore the ability of two-particle point-charge models to reproduce both the solvation free energy and coordination number in TIP3P water. We find that this is possible only with unphysical changes in the nonbonded parameters which create problems in proton hopping simulations. We then construct a classical OH^- model with the charge of oxygen distributed among three auxiliary particles. This model favors a lower coordination number by accepting three hydrogen bonds and weakly donating one. The model was implemented in the MOBHY module of the CHARMM program and was fit to reproduce the experimental aqueous diffusion coefficient of OH^-. This parameterization gave reasonable electrophoretic mobilities and the expected accelerated transport under nanoconfinement.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12161-12170"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764549","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}