The Journal of Physical Chemistry B最新文献

Alpha-synuclein (α-syn) is an intrinsically disorderedprotein(IDP) associated with amyloid formation in neurodegenerative diseases,including Parkinson’s, dementia with Lewy bodies, and multiplesystem atrophy. Disease progression is linked to the transition ofα-syn from native to misfolded conformations, although the mechanismsunderlying this process remain unclear. An effective method for investigatingprotein dynamics is native mass spectrometry, specifically when coupledwith ion mobility-mass spectrometry (IM-MS) to examine differencesin the shape and size of various analytes. In this study, variable-temperatureelectrospray ionization ion mobility-mass spectrometry (vT-ESI-IM-MS)was used to investigate the conformational dynamics of wild-type andA30P α-syn in the presence and absence of five osmolytes trimethylamine-N-oxide (TMAO), urea, guanidine, 1-dodecylguanidine (dodine),and arginine. For both α-syn variants, the abundance of extendedconformers increased with temperature in the absence of osmolytes,consistent with temperature-dependent conformational shifts. Thisstudy shows osmolytes significantly alter conformational distributionsand temperature-dependent responses, with dodine promoting extendedconformations and guanidine producing the lowest abundance of extendedstates. These results demonstrate the utility of vT-ESI-IM-MS forprobing IDP dynamics and highlight the influence of osmolytes on IDPconformational behavior.

The development of solid polymer electrolytes for lithiumbatteriesrequires a molecular-level understanding of how host architectureand additives jointly control ion transport. Here, classical moleculardynamics simulations, complemented by density-functional theory, areused to investigate the independent effects of polyacrylonitrile (PAN)chain length and fluoroethylene carbonate (FEC) plasticizer contenton lithium-ion transport and solvation in the PAN–LiFSI–FECsystem. Increasing the chain length is found to suppress lithium diffusion,as longer chains progressively cage the cation within the nitrilecoordination environment. Incorporation of FEC enhances the ionicconductivity by more than an order of magnitude, saturating over abroad 30–40 wt % range, despite a concurrent increase in bulkdensity that rules out a simple free-volume mechanism. Radial-distributionand residence-time analyses reveal that FEC does not enter the lithiumfirst coordination shell but instead acts as a second-sphere plasticizerthat renders the lithium–polymer coordination dynamically labile;the diffusion coefficient correlates strongly and inversely with thecoordination residence time. Density-functional calculations showthat FEC binds lithium more strongly than the polymer nitrile, demonstratingthat its exclusion from the first shell is entropic and steric ratherthan energetic. These results establish a coordination-dynamics mechanismfor plasticizer-enhanced transport and identify a plasticized intermediate-lengthPAN host as a favorable electrolyte design.

Rare-earth elements (REEs: La–Lu, Y, Sc) are criticaltomodern technology; however, their acquisition, purification, and separationfrom each other can be challenging, and current methods are oftenenvironmentally damaging. Metal-binding polymers are a promising materialclass to improve these methods, but fundamental structure–propertyrelationships have yet to be fully developed. Inspired by nature’suse of solvation- and conformation-driven effects to control metal-bindinginteractions, we hypothesized that modifying the molecular environmentaround the binding sites on metal-chelating polymers could offer away to modify solvation structure and direct these interactions. Specifically,we hypothesized that increasing binding-site hydrophilicity wouldincrease the enthalpic favorability of polymer–metal interactions,while maintaining the entropic driving force of metal-ion dehydration.To test this hypothesis, we synthesized a series of poly(amino acidacrylamides) with systematic changes in the hydrophilicity aroundthe metal-binding sites, using a modular polymer approach to holdkey polymer parameters constant. We then used isothermal titrationcalorimetry (ITC) to measure the solution thermodynamics of polymer–REEbinding. Binding by all polymers in this series was entropically driven─consistentwith substantial solvent reorganization─but binding site hydrophilicitydid not significantly affect binding thermodynamics due to enthalpy–entropycompensation. Interestingly, poly(glutamic acid acrylamide) displayeda distinct binding behavior, possibly driven by reduced solvent reorganizationand larger conformational contributions. In general, lower hydrophilicitywas associated with larger desolvation signatures, which could indicatethat hydrophobic groups more effectively dehydrate the metal ion thanhydrophilic groups. Together, these results demonstrate how polymerstructure can modulate desolvation and control polymer-REE bindingwhile also highlighting thermodynamic constraints that limit straightforwardtuning of binding affinity, thus providing new insights for the designof materials for critical metal purification.

In this work, we evaluate whether computed conformationalensemblesof seven tripeptides─the six C-terminal amidated D/Y/F sequenceisomers and the closely related sequence FFD─are informativeof their self-assembly propensity. Using all-atom molecular dynamics(AA-MD) simulations and intramolecular side-chain dihedral anglesas a collective variable, we calculate conformational free-energylandscapes (FELs) for these sequences. We then introduce a novel methodto numerically characterize the computed FELs and find a correlationbetween thermal conformational accessibility and a sequence’stendency to self-assemble or remain in solution. In addition, we evaluateand rationalize the impact of water model selection on conformationalensembles in terms of peptide-water interaction strengths, and alsoinvestigate the influence of ionization state on conformation. Thepresented methodology implicitly accounts for amino acid sequencecontext, which is a major determinant of divergent properties forsequence isomers. It also has a low associated computational cost,making use of single-molecule simulations to predict supramolecularassembly outcomes. These features are an important advancement towarda general scheme for the theory-informed design of peptide materials.

The human mitochondrial tRNA methyltransferase TRMT10Ccontainsa 41-residue long positively charged α-helix in its N-terminaldomain, interacting with tRNAs from the anticodon to the T-loops.Here, we investigated the flexibility of this N-terminal long α-helixusing comparative molecular dynamics simulations in explicit solventwith three different force fields/water model combinations, alongsidetwo helices of identical length but different sequences: a polyalaninehelix and an AEEEKRK repeat helix. We also expanded our simulationsto three additional helices belonging to the Trm10 family. Five independent1-μs simulations were performed for each system. The human TRMT10Chelix turned out to display heterogeneous dynamics, with a stableα-helical segment (residues 132–139) embedded withinmore flexible regions and this trend was also observed in the humanTrm10 family members. This relatively rigid segment is more hydrophobic,whereas the remaining portion is enriched in charged residues andshows higher conformational variability. The rigid region correspondsto the portion interacting with the cavity formed by tRNA and TRMT10CN-terminal domain. Additional simulations using alternative force-fieldand water-model combinations supported the robustness of the overallflexibility ranking for the AEEEKRK repeat helix and the TRMT10C helix,but it gave force-field-dependent results for the structural dynamicsof the polyalanine helix. Simulations of the N-terminal helices ofother TRMT10C homologues revealed similar flexibility profiles, suggestingthat the observed trends are generalizable across the family. Basedon our results, we suggest that the human TRMT10C helix is tuned tocombine localized rigidity to provide localized structural supportthat helps present the fragile mitochondrial tRNA to the maturationenzymes with overall flexibility for conformational adaptation, facilitatingtRNA positioning and efficient catalysis.

The dynamics of largeand anisotropic molecules embeddedin glass-formingliquids present complex challenges due to the interplay between molecularshape, host–guest interactions, and macroscopic viscosity.In this work, we investigate fluorophenylene isomers (ortho-F and para-F) dissolved in the ortho-terphenyl (OTP) matrix, combining broadband dielectric spectroscopy,differential scanning calorimetry, and rheology to disentangle hostand probe dynamics. While calorimetry reveals a single glass transitiondominated by OTP, dielectric measurements resolve two distinct α-relaxationprocesses: a fast process corresponding to OTP structural relaxationand a slower process associated with probe relaxation, i.e., reorientationof large and anisotropic molecules in a weakly polar matrix. Furthermore,the α-relaxation peak of the guest molecules becomes noticeablynarrower upon dilution in OTP. We attribute this behavior to the dynamichomogenization of the local environment arising from the large sizemismatch between the guest and the host molecules. Mechanical relaxationtimes derived from viscosity match the fast dielectric α-process,indicating that OTP exclusively governs the viscous response. Interestingly,the para-F/OTP mixture shows ideal Debye–Stokes–Einstein(DSE) coupling, whereas ortho-F/OTP exhibits systematicdecoupling, reflecting the importance of probe dipole orientationand anisotropy.

Coarse-grained (CG)water models with explicit electrostaticinteractionsare essential for capturing the dielectric response of biomolecularsystems. However, many CG water models exhibit pronounced freezingartifacts under ambient conditions. Using the SPICA force-field familyas a case study, we examined the influences of charge topology, backgrounddielectric screening (ε_bg), and Lennard–Jones(LJ) interaction strength on the freezing tendency of CG water. Amongthe models examined here, which all reproduce the target density andsurface tension at 298 K, changing the charge topology from a lineardipole to V-shaped geometries did not substantially lower the meltingtemperature (T_m). Instead, T_m was more sensitive to the LJ interaction strength. Reducingε_bg strengthens the electrostatic contribution, allowingthe LJ attraction to be weakened while maintaining the target properties.On this basis, we propose a parametrization framework for introducinga permanent dipole into a nonpolar CG water model while mitigatingits freezing tendency. Using this framework, we developed pSPICA2,which reduces T_m from 384 to 302 K whileretaining accurate density, surface tension, and dielectric responseat 298 K. Although T_m remains above theexperimental value of 273 K in this work, the proposed framework offersa practical route for developing polar CG water models with reducedfreezing artifacts.

Excited-state intramolecularproton transfer (ESIPT)processeshave attracted much attention due to their applications in sensing,imaging, and solid-state optoelectronic devices. The effect of substitutionon ESIPT was studied by synthesizing 2-(4’-(N,N-diethylamino)-2’-hydroxyphenyl)benzimidazole-5-carbonitrile(DEAHBIC). The fluorophore was investigated experimentally in solutionand as a powder sample. Theoretical calculations were performed tounderstand the effect of solvent polarity on the emission behavior.The theoretical studies revealed that not only the shift in equilibriumbut also a reduction in ESIPT decrease the tautomer emission in polarenvironments. The fluorescence quantum yield of DEAHBIC was significantlylower than 2-(2’-hydroxyphenyl)benzimidazole (HBI). The formationof an intramolecular charge-transfer-induced twisted keto form reducedthe fluorescence. Time-resolved fluorescence studies revealed thatthe tautomer emission lifetime was longer than the normal emissionin less polar solvents. In contrast to HBI, in more polar solventsthe lifetime of the normal emission of DEAHBIC was longer than itstautomer emission. Unlike the electron-withdrawing NO₂ group,the cyano substitution reduced ESIPT. In the powder sample, ESIPTwas increased, which enhanced the relative intensity of the tautomeremission, but the overall fluorescence quantum yield was reduced.In addition, ESIPT was also investigated in polymer films. The tautomerfluorescence quantum yield was improved in thin films. Studies inpolymer thin films are also useful for understanding the microenvironmentexperienced by the molecule in the polymer film. The tautomer emissionwavelength red-shifted and the ϕ_T/ϕ_N ratio increased in the order polystyrene (PS) < polysulfone (PSF)< poly(methyl methacrylate) (PMMA) < polyvinyl acetate (PVAc)< polyvinyl chloride (PVC).

We present a new description of large-scale peptide-planedynamicsoccurring primarily in protein loops, based on established symmetryprinciples. As model system we analyze molecular dynamics (MD) simulationsof the Rho GTPase-binding domain of plexin-B1 (RBD). From the MD trajectories,we derive statistical local peptide-plane-related potentials, u(θ, φ), and corresponding probability distributions, P(θ, φ) = exp[−u(θ,φ)]. The polar angles, (θ, φ), describe the orientationof the probe in the protein. The time series of the peptide-plane-flankingdihedrals, (Ψ, Φ), are also derived. Earlier 50–100ns RBD simulations yielded positive-φ free-energy surfaces, u(positive)(θ, φ), spanning the 0 ≤ (θ,φ) ≤ 180° range. To extract maximal informationfrom these statistical functions, we explicitly approximated themby combinations of real Wigner functions, D_L,K, which, like the peptide plane,exhibit D_2h symmetry. Nonpolar A_g and uniquelypolar-vector B_2u terms were found to make the dominantcontributions. Here we use 1 μs RBD simulations. Along withthe previously observed u(positive)(θ, φ)component, a negative-φ component, u(negative)(θ,φ), spanning the θ′ = 180° – θand φ′ = – φ range, also appears. Withinthe overall potential, u(combined)(θ, φ),the two components relate by inversion and rarely interconvert, pointingphenomenologically to slow motion on the 1 μs time scale. Thisbehavior is also evident in the time series of the peptide-plane-flankingdihedrals. The overall potential, u(combined)(θ,φ), is analyzed empirically. We show that A_g andB_2u D_2h symmetry elements are inherent to itsstructure. Based on the results obtained here and in the accompanyingarticle in this issue, we establish a new symmetry-based frameworkfor analyzing local peptide-plane dynamics, grounded in the effectiveD_2h symmetry of the peptide plane. Actual motions are exemplifiedby the canonical type II → type I β-turn crankshaft flipsexecuted by the peptide plane K50–G51 of the L2 loop of theRBD. Broader applications involving diverse peptide-plane restructuringmechanisms are presented in the accompanying article.

Nanoplastics arepervasive environmental contaminantscapable ofcrossing biological barriers and interacting with cell membranes.However, the molecular mechanisms by which they perturb lipid interfacesremain poorly understood. Here, we combine Fourier-transform infraredspectroscopy (FTIR), ultrafast two-dimensional infrared spectroscopy(2D IR), and surface-enhanced infrared absorption (SEIRA) spectroscopyto investigate how anionic polystyrene nanoplastic (NP) particlesmodulate the environment at the lipid–water interface in modellipid membranes by varying composition and ionic environment. Neutralphosphatidylcholine (POPC) and anionic phosphatidylcholine/phosphatidylserine(POPC/POPS) membranes were used to probe the role of membrane chargeon NP-induced interfacial perturbations. FTIR measurements show thatNP-induced dehydration of the lipid headgroup region depends stronglyon membrane composition, with partial dehydration observed in neutralPOPC membranes but negligible changes in anionic POPC/POPS membranes.2D IR spectra show that NPs induce faster H-bond fluctuations, aswater molecules become more labile at the interface. SEIRA measurementsfurther show that these interfacial perturbations are accompaniedby localized changes in the acyl-chain ordering. Addition of Ca²⁺ enhances NP-induced changes to the negatively charged membranes,resulting in hydration dynamics and acyl-chain ordering that resemblethose observed in neutral POPC membranes. These results are consistentwith the hypothesis that interfacial dehydration is an early eventassociated with NP-membrane interactions and highlight the role ofmembrane charge and ionic environment in modulating these interactions.