Energetic analysis of succinic acid in water droplets: insight into the size-dependent solubility of atmospheric nanoparticles

<p>Size-dependent solubility is prevalent in atmospheric nanoparticles, but a molecular level understanding is still insufficient, especially for organic compounds. Here, we performed molecular dynamics simulations to investigate the size dependence of succinic acid solvation on the scale of ~1-4 nm with the potential of mean forces method. Our analyses reveal that the surface preference of succinic acid is stronger for a droplet than the slab of the same size, and the surface propensity is enhanced due to the curvature effect as the droplet becomes smaller. Energetic analyses show that such surface preference is primarily an enthalpic effect in both systems, while the entropic effect further enhances the surface propensity in droplets. On the other hand, with decreasing droplet size, the solubility of succinic acid in the internal bulk volume may decrease, imposing an opposite effect on the size dependence of solubility as compared with the enhanced surface propensity. Meanwhile, structural analyses, however, show that the surface to internal bulk volume ratio increases drastically, especially when considering the surface in respect to succinic acid, e.g., for droplet with radius of 1 nm, the internal bulk volume would be already close to zero for the succinic acid molecule.</p>

Energetic analysis of succinic acid in water droplets: insight into the size-dependent solubility of atmospheric nanoparticles

Size-dependent solubility is prevalent in atmospheric nanoparticles, but a molecular level understanding is still insufficient, especially for organic compounds. Here, we performed molecular dynamics simulations to investigate the size dependence of succinic acid solvation on the scale of ~1–4 nm with the potential of mean forces method. Our analyses reveal that the surface preference of succinic acid is stronger for a droplet than the slab of the same size, and the surface propensity is enhanced due to the curvature effect as the droplet becomes smaller. Energetic analyses show that such surface preference is primarily an enthalpic effect in both systems, while the entropic effect further enhances the surface propensity in droplets. On the other hand, with decreasing droplet size, the solubility of succinic acid in the internal bulk volume may decrease, imposing an opposite effect on the size dependence of solubility as compared with the enhanced surface propensity. Meanwhile, structural analyses, however, show that the surface to internal bulk volume ratio increases drastically, especially when considering the surface in respect to succinic acid, e.g., for droplet with radius of 1 nm, the internal bulk volume would be already close to zero for the succinic acid molecule.

Hydrophobicity of an isobutane dimer in water, methanol and acetonitrile as solvents — A classical molecular dynamics study

The potential of mean forces (PMFs) has been determined for an isobutane dimer in various solvent environments such as water, methanol and acetonitrile at a temperature of 298 K and pressure of 1 bar using GROMACS software. All the molecular dynamics (MD) simulations are carried out using a TIP3P water model under a CHARMM36 forcefield. Following Umbrella Sampling technique, PMFs are calculated and analyzed using Weighted Histogram Analysis Method (WHAM) and coordination number of first solvation shell is extracted for all solvents using radial distribution function. The shape of PMFs contains contact minima, solvent-separated minima and desolvation maxima. The values of contact minima are not affected much by solvent environment and found to be at 0.5377, 0.5480 and 0.5495 nm for water, methanol and acetonitrile respectively. The corresponding energy depths are found −0.9134, −0.7080 and −0.5295 kcalmol[Formula: see text]. The variation observed at solvent-separated minima is noticeable and found at 0.9012, 0.9721 and 0.9151 nm for water, methanol and acetonitrile, respectively. The coordination number of the first solvation shell by taking an isobutane molecule as a reference from their center of mass is found to be 28.1, 16.9 and 14.8 for water, methanol and acetonitrile, respectively. There is a soft hydrophobic interaction between isobutane dimer and solvents like methanol and acetonitrile relative to water, might be due to the presence of competitive methyl group of methanol and acetonitrile in the solvent medium.

Computational Study for the Unbinding Routes of β-N-Acetyl-d-Hexosaminidase Inhibitor: Insight from Steered Molecular Dynamics Simulations

β-N-Acetyl-d-hexosaminidase from Ostrinia furnacalis (OfHex1) is a new target for the design of insecticides. Although some of its inhibitors have been found, there is still no commercial drug available at present. The residence time of the ligand may be important for its pharmacodynamic effect. However, the unbinding routes of ligands from OfHex1 still remain largely unexplored. In the present study, we first simulated the six dissociation routes of N,N,N-trimethyl-d-glucosamine-chitotriomycin (TMG-chitotriomycin, a highly selective inhibitor of OfHex1) from the active pocket of OfHex1 by steered molecular dynamics simulations. By comparing the potential of mean forces (PMFs) of six routes, Route 1 was considered as the most possible route with the lowest energy barrier. Furthermore, the structures of six different states for Route 1 were snapshotted, and the key amino acid residues affecting the dissociated time were analyzed in the unbinding pathway. Moreover, we also analyzed the “open–close” mechanism of Glu368 and Trp448 and found that their conformational changes directly affected the dissociation of TMG-chitotriomycin. Our findings would be helpful to understanding and identifying novel inhibitors against OfHex1 from virtual screening or lead-optimization.

Free energy profiles of ion permeation and doxorubicin translocation in TolC

The outer membrane protein TolC of Escherichia coli forms a channel-tunnel pore spanning the periplasmic space and outer membrane, serving as the main exit duct for bacteria multidrug resistance and protein export. Many aspects of the transport mechanism of TolC are still unclear. Here, we have investigated the substrate permeability and gating mechanism of TolC by calculating the potential of mean forces (PMFs) for transporting sodium ion and doxorubicin through TolC using the adaptive biasing force (ABF) method. The transport mechanism is turned out to be substrate dependent. It is found that the periplasmic gate is required to open for the passage of both Na + and doxorubicin, but the conformational gating does not lead to permeation barrier for Na + at this region. The extracellular loops and K283 residues cause permeation barriers for Na + at the extracellular entrance, but not for doxorubicin due to the extensive interactions between the drug molecule and the protein. TolC exhibits high conformational flexibility during the transport of Na +, while doxorubicin seems to be able to stabilize TolC in the resting state with the periplasmic gate closed. The association of the TolC docking domain of AcrB does not lower the permeation barrier for doxorubicin at the periplasmic gate, while the gate opening induces the dissociation of the TolC–AcrB complex.

The Kirkwood Superposition Approximation, Revisited and reexamined

The Kirkwood superposition approximation (KSA) was originally suggested to obtain a closure to an integral equation for the pair correlation function. It states that the potential of mean force of say, three particles may be approximated by sum of potential of mean forces of pairs of particles. Nowadays, this approximation is widely used, explicitly or implicitly, in many fields unrelated to the problem for which it was suggested.It is argued that the KSA is neither a good approximation nor a bad approximation; it is simply not an approximation at all.