The Journal of Physical Chemistry B最新文献

{"title":"Molecular Structure Refinement of a ß-Heptapeptide Based on Residual Dipolar Couplings: The Challenge of Extracting Structural Information from Measured RDCs.","authors":"Maria Pechlaner, Wilfred F van Gunsteren, Lorna J Smith, Niels Hansen","doi":"10.1021/acs.jpcb.4c06955","DOIUrl":"10.1021/acs.jpcb.4c06955","url":null,"abstract":"<p><p>The experimental determination of residual dipolar couplings (RDCs) rests on sampling the rotational motion of a molecule in an environment that induces a slightly nonuniform, unfortunately immeasurable, orientation distribution of the molecule in solution. Averaging over this slightly nonuniform, anisotropic distribution reduces the size of the dipolar couplings (DCs) from the kHz range to the Hz range for the resulting RDCs by a factor of 10³ to 10⁴. These features hamper the use of measured RDCs to contribute to the structure determination or refinement of (bio)molecules. The commonly used alignment-tensor (<i>AT</i>) methodology assumes that the immeasurable, unknown orientation distribution of the molecule can be expressed in terms of five spherical harmonic functions of order 2. Staying close to experiment, RDCs can, alternatively, be calculated from a molecular simulation by sampling the rotational motion of the molecule (<i>MRS</i> method) or, instead, of a vector (<i>mfv</i>) representing the magnetic field (<i>HRS</i> method). The <i>AT</i> and <i>HRS</i> methods were applied to a β-heptapeptide solvated in methanol, for which 131 NOE atom-atom distance upper bounds and 21 ^<i>3</i><i>J</i>-couplings derived from NMR experiments are available and, in addition, 39 RDC values obtained for the molecule solvated in methanol with polyvinyl acetate added. In methanol at room temperature and pressure, the molecule adopts a relatively stable helical fold. It appears that MD simulation of the molecule in methanol using the GROMOS biomolecular force field already satisfies virtually all experimental data. Application of RDC restraining shows the limitations caused by the assumptions on which the <i>AT</i> and <i>HRS</i> methods rest and suggests that experimentally measured RDCs are less useful for molecular structure determination or refinement than other observable quantities that can be measured by NMR techniques. The results illustrate that in structure determination or refinement of a (bio)molecule based on experimentally measured data, it is mandatory (i) to refrain from the vacuum boundary condition and (ii) from torsional-angle restraints that do not account for the multiplicity of the inverse function of the Karplus relation expressing ³<i>J</i>-couplings in terms of molecular torsional angles, (iii) to allow for Boltzmann-weighted time- or molecule-averaging and, not the least, (iv) to use a force field that has an adequate basis in thermodynamic data of biomolecules.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3131-3158"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622895","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":"Understanding the Role of Solvent Polarity and Amino Acid Composition of Cyclic Peptides in Nanotube Stability","authors":"Rimjhim Moral,&nbsp; and ,&nbsp;Sandip Paul*,&nbsp;","doi":"10.1021/acs.jpcb.5c0040010.1021/acs.jpcb.5c00400","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00400https://doi.org/10.1021/acs.jpcb.5c00400","url":null,"abstract":"<p >Cyclic peptides (CPs) possess the ability to self-assemble into cyclic peptide nanotubes (CPNTs), which find extensive applications in nanotechnology. The formation and stability of these nanotubes are influenced by multiple factors. The present study explores the stability of CPNTs in various solvents with varying polarity, focusing on three specific peptide sequences: D<u>K</u>₄, W<u>L</u>₄, and D<u>L</u>K<u>L</u>₂. Using molecular dynamics simulations, the effect of solvent polarity and peptide composition on the stability of CPNTs is assessed through the determination of electrostatic, van der Waals, and hydrogen-bonding interactions. The binding free energy between adjacent cyclic peptide rings is analyzed via MM/GBSA and MM/PBSA methods, revealing that D<u>L</u>K<u>L</u>₂, an amphiphilic peptide, exhibits greater stability than D<u>K</u>₄ and W<u>L</u>₄ in nonpolar solvents. The introduction of leucine residues in D<u>L</u>K<u>L</u>₂ reduces intramolecular hydrogen bonding and electrostatic interactions, promoting stronger interpeptide backbone hydrogen bonds and maintaining the nanotube’s structural integrity. Hydrogen bond lifetimes, computed using the corresponding time correlation function, indicate the longest-lasting hydrogen bonds occur in all the solvent environments except water, further contributing to the stability of D<u>L</u>K<u>L</u>₂ nanotubes. Additionally, deformation from circularity in the peptide rings, analyzed using ellipticity values, highlights the degree of structural distortion across solvents, with D<u>K</u>₄ showing the highest deviation due to stronger intramolecular interactions. These findings offer valuable insights into the roles of solvent and peptide composition in the self-assembly and stability of CPNTs, which have significant implications for their potential applications in nanotechnology and biomedicine.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 14","pages":"3590–3603 3590–3603"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806807","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 the Therapeutic Ability of Novel Antimicrobial Peptide Dendropsophin 1 and Its Analogues through Membrane Disruption and Monomeric Pore Formation.","authors":"Fahmida Rahman, Sujit Halder, Shamo Rahman, Md Lokman Hossen","doi":"10.1021/acs.jpcb.4c07758","DOIUrl":"10.1021/acs.jpcb.4c07758","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are an alternative source of antibiotics that fight worldwide antibiotic-resistant catastrophes. Dendropsophin 1 (Dc1) is a recently invented novel AMP with 17 amino acid residues obtained from the screen secretion of a frog named <i>Dendropsophus columbianus</i>. Dc1 has two slightly mutated analogues, namely, Dc1.1 and Dc1.2, with improved cationicity and mean amphipathic moment to enhance the selective toxicity against microorganisms. Experimental results indicate that Dc1 and Dc1.1 have similar antimicrobial activity against Gram-negative bacteria <i>Escherichia coli</i> and Gram-positive bacteria <i>Staphylococcus aureus</i>, whereas the synthesized peptide Dc1.2 has shown antimicrobial activity against a wide range of microorganisms. However, the molecular level details of the peptide-membrane interaction and the corresponding changes in the peptide structure remain elusive. In this study, we investigate the bacterial membrane disruption capability of these AMPs by running a total of 14.2 μs long molecular dynamics (MD) simulations. Our findings suggest that all three peptides affect the upper layer of the membrane with different degrees of disruption. After penetration, Dc1 and Dc1.2 retain stable α-helices in the core region, indicating the potential to disrupt the second layer. However, secondary structure analysis shows that Dc1.2 attains extended helical regions on the C-terminus, suggesting it as the superior candidate among the analogues to have the potential of stable pore formation, leading to bacterial cell death. To speed up our study, we adopt a one-transmembrane configuration of Dc1, Dc1.1, and Dc1.2 and find toroidal pores with subsequent water leakage for Dc1.2.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3171-3182"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397499","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":"Impact of Polydispersity on Phase Separation: Insights from Polyethylene Glycol and Dextran Mixtures.","authors":"Akari Kamo, Arash Nikoubashman, Miho Yanagisawa","doi":"10.1021/acs.jpcb.4c08640","DOIUrl":"10.1021/acs.jpcb.4c08640","url":null,"abstract":"<p><p>The dynamic formation of (bio)molecular condensates has emerged as a key regulatory mechanism in cellular processes. Concepts from polymer physics can provide valuable insights into the underlying mechanisms and properties of these condensates. While stoichiometric interactions between chemically distinct molecules have traditionally been the primary focus for understanding and predicting the equilibrium behavior, recent attention has turned to the role of molecular diversity, particularly the interplay between molecules of similar types but varying chain lengths. To mimic such cellular conditions, we investigated the impact of molecular weight polydispersity using polyethylene glycol (PEG) and dextran (Dex) solutions through experiments and molecular simulations. Our findings reveal that polydisperse systems, which contain a higher fraction of short-chain components, exhibit a narrower two-phase region, along with reduced concentration differences and interfacial tension between the coexisting polymer-rich and polymer-poor phases. In these systems, the Dex-rich phase is enriched with longer Dex chains compared to the PEG-rich phase, with a gradual transition in chain length across their interface. However, polydispersity has no significant effects on the critical concentration and critical exponents. Finally, our study of condensation kinetics demonstrates that phase separation is not limited by the nucleation rate but instead by the diffusion-driven aggregation of polymers.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3263-3271"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622893","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":"Linear-Limit Aging Times of Three Monoalcohols.","authors":"Jan Philipp Gabriel, Jeppe C Dyre, Tina Hecksher","doi":"10.1021/acs.jpcb.5c00698","DOIUrl":"10.1021/acs.jpcb.5c00698","url":null,"abstract":"<p><p>This paper presents data on the physical aging of three monoalcohols, 2-ethyl-1-butanol, 5-methyl-2-hexanol, and 1-phenyl-1-propanol. Aging is studied by monitoring the dielectric loss at a fixed frequency in the kHz range following temperature jumps of a few Kelvin's magnitude, starting from states of equilibrium. The three alcohols differ in Debye relaxation strength and how much the Debye process is separated from the α process. We first demonstrate that single-parameter aging describes all data well and proceed to utilize this fact to identify the linear-limit normalized aging relaxation functions. From the Laplace transform of these functions, the linear-limit aging loss-peak angular frequency defines the inverse of the linear aging relaxation time. This allows for a comparison to the temperature dependence of the Debye and α dielectric relaxation times of the three monoalcohols. We conclude that the aging response for 5-methyl-2-hexanol and 2-ethyl-1-butanol follows the α relaxation, not the Debye process; no firm conclusion can be reached for 1-phenyl-1-propanol because its Debye and α processes are too close to be reliably distinguished.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3272-3279"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646552","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 Sequence Landscape of Peptide Fibrillization with a Bottom-Up Coarse-Grained Model","authors":"Evan Pretti,&nbsp; and ,&nbsp;M. Scott Shell*,&nbsp;","doi":"10.1021/acs.jpcb.4c0724810.1021/acs.jpcb.4c07248","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c07248https://doi.org/10.1021/acs.jpcb.4c07248","url":null,"abstract":"<p >Molecular insight into amyloid aggregation is crucial for understanding the details of protein fibril nucleation and growth, which play a significant role in a wide range of proteinopathies. The length and time scales for fibrillization make its computational study an intrinsically multiscale problem, necessitating the use of coarse-grained modeling. A wide variety of coarse-grained models for peptides have been proposed, often parametrized with a combination of top-down and bottom-up approaches. Here, we present a predictive, sequence-transferable bottom-up coarse-grained model, systematically developed using only information from atomistic simulations by applying an extended-ensemble relative entropy minimization technique. The resulting model is capable of accurately recovering conformational properties of peptides constructed from a reduced alphabet of amino acids, of predicting secondary structures of isolated and interacting peptides from their sequences alone, and of simulating aggregation of peptides that have been experimentally characterized as amyloidogenic. Finally, we couple such coarse-grained simulations with a genetic algorithm to characterize the sequence space of the reduced alphabet and identify features of sequences for which ordered fibrillar states are both thermodynamically favorable and kinetically accessible.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 14","pages":"3559–3570 3559–3570"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806806","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":"Apparent Kinetic Isotope Effects for Multi-Step Steady-State Reactions.","authors":"Ian H Williams","doi":"10.1021/acs.jpcb.5c00561","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c00561","url":null,"abstract":"<p><p>The apparent kinetic isotope effect (KIE) for a multistep steady-state reaction can be expressed simply as a sum of terms, one for each transition state (TS) in the serial sequence, each of which is the product of the KIE for an individual TS (with respect to a common reference state) and a weighting factor, which is the degree of kinetic significance for that TS. This requires knowledge of the relative Gibbs energies of the sequential TSs but not of any intermediates, and it involves a much simpler expression than the conventional method for analysis of KIEs for enzyme reactions. A numerical example is presented to illustrate how the same apparent KIE may result from numerous combinations of individual KIEs and weighting factors. It is proposed that computed apparent KIEs should be compared directly with experimentally observed KIEs rather than with derived intrinsic KIEs of possibly dubious validity. The results of DFT calculations for an S_N1 nucleophilic displacement are presented to show how the apparent KIE varies, as the relative concentration of the nucleophilic species ranges from 0.1 to 10, between limiting values corresponding to either the first or second step being completely rate limiting.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727034","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":"Understanding Anti-Polyelectrolyte Effect in Polyzwitterions Using Coarse-Grained Molecular Dynamics Simulations.","authors":"Akshay Chauhan, Srabanti Chaudhury","doi":"10.1021/acs.jpcb.4c07728","DOIUrl":"10.1021/acs.jpcb.4c07728","url":null,"abstract":"<p><p>Polyzwitterions (PZs)─polymers bearing both positive and negative charges within each repeating unit─exhibit an unusual antipolyelectrolyte effect where their solubility and viscosity increase upon the addition of salt, contrary to typical polyelectrolytes. As model synthetic analogues of intrinsically disordered proteins, PZs in dilute aqueous solutions are expected to adopt either globular or random coil conformations, with salt addition influencing these structures. We employed coarse-grained Langevin dynamics simulations to investigate how structural parameters─specifically, the spacing between dipolar side chains (<i>d</i>), and the overall polymer chain length (<i>N</i>)─affect the conformational properties of polyzwitterions in salt solutions. Our simulations reveal that added salt leads to nonmonotonic changes in the polymer's radius of gyration, exhibiting both antipolyelectrolyte and polyelectrolyte effects depending on the salt concentration. This behavior is attributed to charge regulation and screening of dipole-dipole interactions by ions. Understanding and controlling the conformations of PZs in aqueous solutions by adjusting salt concentration is of paramount interest for applications in antimicrobial materials, antifouling coatings, drug delivery, membranes, and polymer electrolytes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"3253-3262"},"PeriodicalIF":2.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646558","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":"Regulation of Protein Transport in Functionalized PET Nanopores.","authors":"Juanhua Kong, Rana Jahani, Haiyan Zheng, Shuo Zhou, Jun Chen, Sathishkumar Munusamy, Youwen Zhang, Xiyun Guan","doi":"10.1021/acs.jpcb.5c01036","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c01036","url":null,"abstract":"<p><p>Facilitated translocation is a critical mechanism for transporting substances in biological systems, where molecular and ionic species move across the biological membrane with the help of specific transmembrane protein ion channels. In this work, we systematically examined protein transport in three poly(ethylene terephthalate) (PET) nanopores modified with different types of surface functions (hydroxyl, phenyl, and amine). We found that the event signature as well as the kinetics and thermodynamics of protein movement in the PET nanopore varied significantly with the change in the surface function in the pore. In addition to the electrophoretic effect, other factors such as diffusion, electro-osmotic effect, ion selectivity of the channel, and affinity strength between the protein species and the surface functional group of the nanopore also play significant roles in the protein transport. Although properly functionalized individual PET nanopores can be used as stochastic elements for rapid protein differentiation and characterization, enhanced resolution and accuracy could be accomplished by employing an array of PET nanopores having different inner surface functional groups to characterize proteins based on their collective responses. Given the important roles proteins play in living organisms and their applications as biomarkers in early disease diagnosis and prognosis, the pattern-recognition solid-state nanopore-sensing strategy for protein detection and characterization developed in this work may find useful applications in various fields.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727104","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":"Human Serum Albumin Loaded with Fatty Acids Reveals Complex Protein-Ligand Thermodynamics and Boleadora-Type Solution Dynamics Leading to Gelation.","authors":"Jörg Reichenwallner, Sebastian Michler, Christian Schwieger, Dariush Hinderberger","doi":"10.1021/acs.jpcb.4c08717","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c08717","url":null,"abstract":"<p><p>Using an electron paramagnetic resonance (EPR) spectroscopic strategy that has been developed for core-shell polymers, the complexity of the binding of fatty acids to human serum albumin (HSA) is characterized in detail. We unravel the internal dynamics of HSA solutions with fatty acids by applying continuous wave EPR (CW EPR) from which we derive a consistent thermodynamic interpretation about fatty acid interactions with HSA in the investigated temperature range of 5-97 °C. Additionally, data from CW EPR are corroborated by dynamic light scattering (DLS), differential scanning calorimetry (DSC) and nanoscale distance measurements using double electron-electron resonance (DEER) spectroscopy. We discuss our data in light of decades of biophysical studies on albumin and aim at drawing a complete functional and dynamic picture of HSA \"at work\". This picture suggests that HSA is built from modular, rotationally decoupled domains that resemble an entangled three-piece <i>boleadora</i> in solution.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726977","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}