The Journal of Physical Chemistry B最新文献

We use molecular dynamics simulations to investigate the influence of the hydrogen bond (HB) catching agent dimethyl sulfoxide (DMSO) on the HB network in the hydroxy-functionalized ionic liquid (IL) 1-(4-hydroxybutyl)pyridinium bis(trifluoromethanesulfonyl)imide [HOC₄Py][NTf₂]. Three characteristic HBs are observed: between cations and anions (c-a), between two cations (c-c), and between cations and DMSO molecules (c-m). We quantify the thermodynamic stability of all HB species using a van ’t Hoff analysis, observing that the IL HB network is significantly disrupted by the addition of DMSO. At low DMSO concentrations, stable (c-m) HBs tether DMSO molecules to the cations, leading to their molecular-level dispersion within the IL phase. Generally, the weakest HBs are found between cations and anions, while (c-m) HBs are stronger than (c-c) HBs. Adding DMSO, however, is also affecting the equilibria involving (c-m) HBs due to a competition of hydrogen bonded DMSO with energetically favorable DMSO–DMSO contacts. HB population correlation functions are used to study the HB kinetics, which reflect the relative thermodynamic stability of HBs and scale excellently with the viscosity. Adding DMSO leads to a strong decrease in the viscosity of the simulated mixture, which is in reasonable agreement with available experimental data.

Precise identification and quantification of amino acids are crucial for numerous biological applications. A significant challenge in the development of high-throughput, cost-effective nanopore protein sequencing technology is the rapid translocation of protein through the nanopore, which hinders accurate sequencing. In this study, we explore the potential of nanopore constructed from a novel two-dimensional (2D) material MoSi₂N₄ in decelerating the velocity of protein translocation using molecular dynamics simulations. The translocation velocity of the peptide through the MoSi₂N₄ nanopore can be reduced by nearly an order of magnitude compared to the MoS₂ nanopore. Systematic analysis reveals that this reduction is due to stronger interaction between the peptide and MoSi₂N₄ membrane surface, particularly for aromatic residues, as they contain aromatic rings composed of relatively nonpolar C-C and C-H bonds. By adjusting the proportion of aromatic residues in peptides, further control over peptide translocation velocity can be achieved. Additionally, the system validates the feasibility of using an appropriate nanopore diameter for protein sequencing. The theoretical investigations presented herein suggest a potential method for manipulating protein translocation kinetics, promising more effective and economical advancements in nanopore protein sequencing technology.

Conformational analysis of poly(trimethylene carbonate) (PTMC) and poly(butylene carbonate) (PBC) was conducted. The most stable conformations in the spacers, O(CH₂)_yO, of PTMC (y = 3) and PBC (y = 4) were found to be tg^±g^±t and tg^±tg^∓t, respectively. The former conformation leads to a long zigzag form for PTMC, while the latter extends the PBC chain along the molecular axis. The O–C and OC–CC bonds in the PTMC spacer prefer trans and gauche conformations, respectively, while the O–C, OC–CC, and CC–CC bonds of PBC show trans, gauche, and trans preferences, respectively. The characteristic ratios of PTMC and PBC in a nonpolar environment at 25 °C were evaluated to be 6.89 and 8.27, respectively, significantly larger than those of poly(ethylene carbonate) (PEC, 2.42) and head-to-tail isotactic poly(propylene carbonate) (PPC, 2.36). As the spacer length increases (PEC, PPC → PTMC → PBC), the negative charge on the carbonate group becomes delocalized, reducing interchain electrostatic repulsions. Consequently, PEC and PPC remain amorphous, whereas PTMC and PBC can only crystallize with difficulty. However, the weak interchain attractions in both crystals result in low enthalpies of fusion, and, correspondingly, relatively low melting points.

Diffusion at the molecular level involves random collisions between particles, the structure of local microscopic environments, and interactions among the molecules involved. Sampling all of these aspects, along with correcting for finite-size effects, can make the calculation of infinitely dilute diffusion coefficients computationally difficult. We present a new approach for estimating the translational diffusion coefficient of biomolecular structures by encapsulating these driving forces of diffusion through piecewise assembly of the component residues of the protein structure. By linking the local chemistry of a solvent-exposed patch of a molecule to its contribution to the overall hydrodynamic radius, an accurate prediction of the computationally and experimentally comparable diffusion coefficients can be constructed following a solvent-excluded surface area calculation. We demonstrate that the resulting predictions for diffusion coefficients from peptides through to protein structures are comparable to explicit molecular simulations and improve on statistical mass-based predictions, which tend to rely on limited training data. As this approach uses the chemical identity of molecular structures, we find that it is able to predict and identify differences in diffusivity for structures that would be indistinguishable by mass information alone.

Nanosized dispersions of the bicontinuous cubic phase (cubosomes) are emerging carriers for drug delivery. These particles possess well-defined internal structures composed of highly-curved lipid bilayers that can accommodate significant drug payloads. Although cubosomes present promising potential for drug delivery, their physicochemical properties and interactions with cell membranes have not yet been fully understood. To clarify the interactions of the cubosomes with cell membranes, we investigated the changes in the structural and cubic membranes of monoolein (MO) cubosomes when mixed with model cell membranes at different phase states using time-resolved small-angle X-ray scattering (TR-SAXS), cryogenic transmission electron microscopy (cryo-TEM), and fluorescence spectroscopy. TR-SAXS results showed that the cubosomes gradually transitioned from the Im3m phase to the lamellar phase after interacting with the liposomes. The time of the structural change of the cubic phase to the lamellar phase was influenced by the fluidity of the liposome bilayers. Mixing the cubosomes with fluid membrane liposomes required less time to transition to the lamellar phase and vice versa. Cryo-TEM images showed that the well-defined internal structure of the cubosomes disappeared, leaving behind lamellar vesicles after the interaction, further confirming the TR-SAXS results. Laurdan fluorescence probe was used to assess the membrane polarity changes occurring to both the cubosomes and liposomes during the interaction. Examination of the normalized fluorescence intensity of the probed cubosomes showed decreasing intensity, followed by a recovery of intensity, which could indicate the disintegration of the cubic membrane and the formation of a mixed membrane. Also, the kinetics of the disintegration of the cubic phase did not seem to be influenced by the composition of the liposomes, which was in line with the normalized SAXS intensity results. Assessing the generalized polarization (GP₃₄₀) values of the cubosomes and liposomes after mixing revealed that the fluidity and membrane hydration states of the cubosomes and liposomes transitioned to resemble their counterpart, confirming the exchange of material between the particles. Over time, the hydration states of the cubosomes and liposomes equilibrated toward an intermediate state between the two. The time needed to reach the final intermediate state was influenced by the membrane fluidity and hydration of the liposomes, more particularly the difference in GP₃₄₀ values and their membrane phase state. These results highlight the importance of examination of the cubic membrane conditions, such as membrane polarity, and their implications on the changes in the cubic structure during the interaction with liposomal membranes.

We use molecular dynamics simulations to investigate the influence of the hydrogen bond (HB) catching agent dimethyl sulfoxide (DMSO) on the HB network in the hydroxy-functionalized ionic liquid (IL) 1-(4-hydroxybutyl)pyridinium bis(trifluoromethanesulfonyl)imide [HOC₄Py][NTf₂]. Three characteristic HBs are observed: between cations and anions (c-a), between two cations (c-c), and between cations and DMSO molecules (c-m). We quantify the thermodynamic stability of all HB species using a van 't Hoff analysis, observing that the IL HB network is significantly disrupted by the addition of DMSO. At low DMSO concentrations, stable (c-m) HBs tether DMSO molecules to the cations, leading to their molecular-level dispersion within the IL phase. Generally, the weakest HBs are found between cations and anions, while (c-m) HBs are stronger than (c-c) HBs. Adding DMSO, however, is also affecting the equilibria involving (c-m) HBs due to a competition of hydrogen bonded DMSO with energetically favorable DMSO-DMSO contacts. HB population correlation functions are used to study the HB kinetics, which reflect the relative thermodynamic stability of HBs and scale excellently with the viscosity. Adding DMSO leads to a strong decrease in the viscosity of the simulated mixture, which is in reasonable agreement with available experimental data.

Diffusion at the molecular level involves random collisions between particles, the structure of local microscopic environments, and interactions among the molecules involved. Sampling all of these aspects, along with correcting for finite-size effects, can make the calculation of infinitely dilute diffusion coefficients computationally difficult. We present a new approach for estimating the translational diffusion coefficient of biomolecular structures by encapsulating these driving forces of diffusion through piecewise assembly of the component residues of the protein structure. By linking the local chemistry of a solvent-exposed patch of a molecule to its contribution to the overall hydrodynamic radius, an accurate prediction of the computationally and experimentally comparable diffusion coefficients can be constructed following a solvent-excluded surface area calculation. We demonstrate that the resulting predictions for diffusion coefficients from peptides through to protein structures are comparable to explicit molecular simulations and improve on statistical mass-based predictions, which tend to rely on limited training data. As this approach uses the chemical identity of molecular structures, we find that it is able to predict and identify differences in diffusivity for structures that would be indistinguishable by mass information alone.

The effect of metal ions on DNA base pairs is crucial for understanding the molecular mechanisms underlying metal-ion-associated gene mutations and has broad applications across various fields. We investigated the interaction between silver ions (Ag⁺) and DNA using single-molecule magnetic tweezers (MT), atomic force microscopy (AFM), and dynamic light scattering (DLS). Our findings reveal that monovalent Ag⁺ can compact DNA directly even at very low concentrations, unlike canonical monovalent ions such as sodium and potassium, which have no effect. We attribute this to the specific binding of Ag⁺ to DNA. For both double-stranded DNA (ds-DNA) and single-stranded DNA (ss-DNA), the critical condensing force (Fc) induced by Ag⁺ initially increases with cationic concentration, reaches a maximum value, and then decreases. We found that the variation in condensing force is due to the rise and fall of silver ions associated with DNA, which is different from the monotonous increase of associated regular cations such as La³⁺ or CoHex³⁺. Notably, the condensing forces for partially denatured DNA by DMSO (including ss-DNA) are larger than those for ds-DNA under the same conditions.

Conformational analysis of poly(trimethylene carbonate) (PTMC) and poly(butylene carbonate) (PBC) was conducted. The most stable conformations in the spacers, O(CH₂)_yO, of PTMC (y = 3) and PBC (y = 4) were found to be tg^±g^±t and tg^±tg^∓t, respectively. The former conformation leads to a long zigzag form for PTMC, while the latter extends the PBC chain along the molecular axis. The O-C and OC-CC bonds in the PTMC spacer prefer trans and gauche conformations, respectively, while the O-C, OC-CC, and CC-CC bonds of PBC show trans, gauche, and trans preferences, respectively. The characteristic ratios of PTMC and PBC in a nonpolar environment at 25 °C were evaluated to be 6.89 and 8.27, respectively, significantly larger than those of poly(ethylene carbonate) (PEC, 2.42) and head-to-tail isotactic poly(propylene carbonate) (PPC, 2.36). As the spacer length increases (PEC, PPC → PTMC → PBC), the negative charge on the carbonate group becomes delocalized, reducing interchain electrostatic repulsions. Consequently, PEC and PPC remain amorphous, whereas PTMC and PBC can only crystallize with difficulty. However, the weak interchain attractions in both crystals result in low enthalpies of fusion, and, correspondingly, relatively low melting points.

Precise identification and quantification of amino acids are crucial for numerous biological applications. A significant challenge in the development of high-throughput, cost-effective nanopore protein sequencing technology is the rapid translocation of protein through the nanopore, which hinders accurate sequencing. In this study, we explore the potential of nanopore constructed from a novel two-dimensional (2D) material MoSi₂N₄ in decelerating the velocity of protein translocation using molecular dynamics simulations. The translocation velocity of the peptide through the MoSi₂N₄ nanopore can be reduced by nearly an order of magnitude compared to the MoS₂ nanopore. Systematic analysis reveals that this reduction is due to stronger interaction between the peptide and MoSi₂N₄ membrane surface, particularly for aromatic residues, as they contain aromatic rings composed of relatively nonpolar C–C and C–H bonds. By adjusting the proportion of aromatic residues in peptides, further control over peptide translocation velocity can be achieved. Additionally, the system validates the feasibility of using an appropriate nanopore diameter for protein sequencing. The theoretical investigations presented herein suggest a potential method for manipulating protein translocation kinetics, promising more effective and economical advancements in nanopore protein sequencing technology.