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[FeFe]‐hydrogenases are capable of reducing protons at a high rate. However, molecular oxygen (O2) induces the degradation of their catalytic cofactor, the H‐cluster, which consists of a cubane [4Fe4S] subcluster (4FeH) and a unique diiron moiety (2FeH). Previous attempts to prevent O2‐induced damage have focused on enhancing the protein's sieving effect for O2 by blocking the hydrophobic gas channels that connect the protein surface and the 2FeH. In this study, we aimed to block an O2 diffusion pathway and shield 4FeH instead. Molecular dynamics (MD) simulations identified a novel water channel (WH) surrounding the H‐cluster. As this hydrophilic path may be accessible for O2 molecules we applied site‐directed mutagenesis targeting amino acids along WH in proximity to 4FeH to block O2 diffusion. Protein film electrochemistry experiments demonstrate increased O2 stabilities for variants G302S and S357T, and MD simulations based on high‐resolution crystal structures confirmed an enhanced local sieving effect for O2 in the environment of the 4FeH in both cases. The results strongly suggest that, in wild type proteins, O2 diffuses from the 4FeH to the 2FeH. These results reveal new strategies for improving the O2 stability of [FeFe]‐hydrogenases by focusing on the O2 diffusion network near the active site. [ABSTRACT FROM AUTHOR]

Here we report synthetic monosaccharide channels built with shape‐persistent organic cages, porphyrin boxes (PBs), that allow facile transmembrane transport of glucose and fructose through their windows. PBs show a much higher transport rate for glucose and fructose over disaccharides such as sucrose, as evidenced by intravesicular enzyme assays and molecular dynamics simulations. The transport rate can be modulated by changing the length of the alkyl chains decorating the cage windows. Insertion of a linear pillar ligand into the cavity of PBs blocks the monosaccharide transport. In vitro cell experiment shows that PBs transport glucose across the living‐cell membrane and enhance cell viability when the natural glucose transporter GLUT1 is blocked. Time‐dependent live‐cell imaging and MTT assays confirm the cyto‐compatibility of PBs. The monosaccharide‐selective transport ability of PBs is reminiscent of natural glucose transporters (GLUTs), which are crucial for numerous biological functions. [ABSTRACT FROM AUTHOR]

The solid-liquid coexistence of a Lennard-Jones fluid confined in slit pores of variable pore size, H, is studied using molecular dynamics simulations. Three-stage pseudo-supercritical transformation path of Grochola [J. Chem. Phys. 120(5), 2122 (2004)] and multiple histogram reweighting are employed for the confined system, for various pore sizes ranging from 20 to 5 molecular diameters, to compute the solid-liquid coexistence. The Gibbs free energy difference is evaluated using thermodynamic integration method by connecting solid-liquid phases under confinement via one or more intermediate states without any first order phase transition among them. Thermodynamic melting temperature is found to oscillate with wall separation, which is in agreement with the behavior seen for kinetic melting temperature evaluated in an earlier study. However, thermodynamic melting temperature for almost all wall separations is higher than the bulk case, which is contrary to the behavior seen for the kinetic melting temperature. The oscillation founds to decay at around H = 12, and beyond that pore size dependency of the shift in melting point is well represented by the Gibbs-Thompson equation. [ABSTRACT FROM AUTHOR]

The anomalies properties of water have been interpreted theoretically using several all-atom and coarse-grained water models. Here we use a robust and traditional free energy approach to develop the solid-liquid coexistence curve for water using coarse-grained monatomic mW and machine-learned bond order potential (ML-BOP) water models. We employ the pseudo-supercritical thermodynamic path in combining multiple histogram reweighting (MHR) and Gibbs-Duhem integration. The ML-BOP model has a broad density-temperature hysteresis loop and shows lower maximum and minimum densities as compared to the mW model. The computed excess Helmholtz free energy and the Gibbs free energy at the approximate melting temperature are higher for the ML-BOP model in comparison with the mW model. The pressure dependence fusion curve for both water models aligns with the literature. This analysis indicates that the free energy method accurately captures the solid-liquid transformation and the thermodynamic melting point of water. [Display omitted] [ABSTRACT FROM AUTHOR]