The Journal of Physical Chemistry B最新文献

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.

Computational approaches can provide details of molecular mechanisms in a crowded environment inside cells. Protein docking predicts stable configurations of molecular complexes, which correspond to deep energy minima. Systematic docking approaches, such as those based on fast Fourier transform (FFT), also map the entire intermolecular energy landscape by determining the position and depth of the full spectrum of the energy minima. Such mapping allows speeding up simulations by precalculating the intermolecular energy values. Our earlier study combined FFT docking with the Monte Carlo protocol, enabling simulation of cell-size, crowded protein systems with seconds, and longer trajectories at atomic resolution, several orders of magnitude longer than those achievable by alternative approaches. In this study, we present a further drastic extension of the modeling capabilities by parallelized implementation of the simulation protocol. The procedure was applied to a panel of Death Fold Domains that form nucleated polymers in human innate immune signaling, recapitulating their homooligomerization tendencies and providing insights into the molecular mechanisms of polymer nucleation. The parallelized protocol allows extension of the simulation trajectories by orders of magnitude beyond the previously reported implementation, reaching into the uncharted territory of atomic resolution simulation of cell-sized systems.

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.

Perceiving a suitably tuned aqueous solution to unravel water's liquid-liquid critical point (LLCP) has become challenging. In this work, we investigated the structures of light and heavy water in the presence of MgCl₂ using excess infrared spectroscopy and density functional theory calculations. The excess spectroscopy enabled us to differentiate the low-density liquid (LDL) water from the other liquid domains of pure water and reveal the new interaction modes between water and the ions. The addition of salt decreases and then increases the population of LDL in aqueous solutions. At the concentrations of 0.4 M in H₂O and 0.6 M in D₂O, the LDL structures undergo the most significant disruption under ambient conditions in the bulk phase. Furthermore, threshold concentrations of 1 and 1.3 M for light and heavy water, respectively, were found to induce higher LDL populations. The current investigation sheds light on the intriguing liquid-liquid phase transition (LLPT) and the LLCP of water.

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: DK₄, WL₄, and DLKL₂. 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 DLKL₂, an amphiphilic peptide, exhibits greater stability than DK₄ and WL₄ in nonpolar solvents. The introduction of leucine residues in DLKL₂ 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 DLKL₂ nanotubes. Additionally, deformation from circularity in the peptide rings, analyzed using ellipticity values, highlights the degree of structural distortion across solvents, with DK₄ 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.

This article presents experimental characterization information and synchrotron X-ray scattering measurements on a set of novel O- and S-substituted phosphonium-based ionic liquids (ILs) all coupled with the bis(fluorosulfonyl)imide (FSI^-) anion. The ILs include the ethoxyethyltriethylphosphonium (P_222(2O2)⁺) and triethyl[2-(ethylthio)ethyl]phosphonium (P_222(2S2)⁺) cations, and we contrast results on these with those for unsubstituted triethylpentylphosphonium (P₂₂₂₅⁺). The article also introduces a physics-based protocol that combines classical force field studies on larger simulation boxes with classical and first-principles studies on smaller boxes. The method produces significantly improved S(q) functions in the regime which in prior publications we have associated with inter- and intraionic adjacency correlations. By understanding which shorter-range structural changes improve S(q) in the q-regime of interest, we are also able to pinpoint specific deficiencies in the classical force field model. The approach we take should be quite general and could help study other complex liquids on different length scales.

We present a structural characterization of a low-transition-temperature mixture (LTTM), consisting of thymol and carvacrol, at an equimolar ratio. Carvacrol and thymol are natural regioisomers of terpenes. When combined at an equimolar ratio, they form a liquid mixture at room temperature, with supercooling capability and glass transition at ca. 210 K. Using small- and wide-angle X-ray scattering and molecular dynamics, we describe the structural complexity within this system. X-ray scattering reveals a low-Q peak at around 0.6 Å^-1, indicating the existence of mesoscale structural heterogeneities, likely related to the segregation of polar moieties engaged in hydrogen bond (HB) interactions within an aromatic, apolar matrix. These polar interactions are predominantly a result of HBs involving thymol as the HB donor species. The liquid structure is also driven by O-H···π interactions, prevalently due to the ability of the carvacrol π-site to engage in this type of weak interaction as a HB acceptor. Besides, dispersive interactions affect the local arrangement of molecules, with a propensity of carvacrol rings to orient their first neighbors with a perpendicular orientation, while thymol tends to induce a closer approach of other thymol molecules with a preferential parallel alignment. Overall, we observed a complex structural arrangement driven by the interplay of both conventional and weak hydrogen bond interactions, with the aromatic nature of the compounds playing a pivotal role in shaping the system's architecture. Carvacrol and thymol, despite being very similar compounds, are characterized by distinctly different behavior in terms of the interactions they engage in with their neighbors, likely due to the different steric hindrance experienced by their hydroxyl groups, which are close to either a small methyl or a bulky isopropyl group, respectively. Such observations can provide useful hints to develop new solvents with tailored properties.

It is well-known that ionic liquids (ILs) can alter the structural stability of proteins. The change in protein conformation is closely related to the interaction between the protein residue and ILs. To probe the impact of hydrophobic interactions on protein stability in ILs, we conducted molecular dynamic simulations and compared the unfolding process of two proteins, the wild-type villin headpiece protein HP35 and its doubly mutant form HP35NN which contains two hydrophobic norleucine (NLE) substitutions at Lys24/29, in hydrated 1-butyl-3-methylimidazolium chloride ([BMIM]Cl). By sampling at a long time scale, the denaturation ability of ILs was well captured. Specifically, HP35NN exhibits greater structural instability than HP35, characterized by the unfolding of helix-3 where the mutated hydrophobic residues are located. These findings highlight the thermodynamic instability of the protein caused by the mutation of two hydrophobic residues in the ILs. By evaluating the hydration kinetics of helix-3 with ILs, we found that the intramolecular hydrogen bonds of HP35NN were broken. At the same time, HP35NN binds to more ILs through hydrophobic interactions. Therefore, we propose that the hydrophobic interaction between ILs and the mutated hydrophobic residue plays a crucial role in the denaturation of HP35NN. The stability comparison and verification of the alkyl chain model of hydrophobic residues in ILs also further prove the instability of hydrophobic residue mutation in ILs. These findings may provide valuable basic information for understanding the effect of ILs on the conformational stability of proteins.

Quantum chemical methods and time-resolved laser spectroscopy are employed to elucidate ultrafast charge-separation processes in triphenylamine (TPA) derivatives upon photoexcitation. When changing the ambient solvent from non-electron-accepting to electron-acceptor solvents, such as chloroform, a vastly extended and multifaceted photochemistry of TPA derivatives is observed. Following initial excitation, two concurrent charge-transfer processes are identified. When the TPA derivative and solvent molecules are arranged in a configuration that favors efficient electron transfer, charge separation occurs immediately, leading to the formation of a radical cation of the TPA derivative. This highly reactive species can subsequently combine with other TPA derivative molecules to yield a dimeric species. Alternatively, if the molecular positioning upon photoexcitation is not optimal, relaxation back to the S₁ state occurs. From this state, an electron transfer process leads to the formation of a charge-transfer complex, where the negatively charged solvent molecule remains closely associated with the positively charged TPA derivative. Within 30 ps, charge recombination occurs in this complex, resulting in the formation of triplet states. This transition to the triplet state is driven by a lower reaction barrier for charge separation compared to that for the formation of the singlet state.

Vapor-liquid equilibrium (VLE) data of fragrance components are crucial for product development and separation processes. However, experimentally obtaining these data can often be a high-cost and challenging task. In order to address this issue, simulations of VLE data using molecular dynamics (MD) methods have gained attention, though there are still relatively few studies about the vapor-liquid equilibrium calculations of fragrance components using MD. In this study, we focused on a mixture of d-limonene and 1-pentanol as representative components and conducted MD simulations. The VLE data obtained by varying the molar fraction of d-limonene, including x-y phase diagrams and activity coefficients, showed a high degree of agreement with the experimental data. Additionally, an analysis of the density profiles on a molecular level revealed a slight increase in the concentration of 1-pentanol at the vapor-liquid interface.