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Molecular simulations and free-energy calculations suggest conformation-dependent anion binding to a cytoplasmic site as a mechanism for Na+/K+-ATPase ion selectivity.

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Na+/K+-ATPase transports Na+ and K+ ions across the cell membrane via an ion-binding site becoming alternatively accessible to the intra- and extracellular milieu by conformational transitions that confer marked changes in ion-binding stoichiometry and selectivity. To probe the mechanism of these changes, we used molecular simulation and free-energy perturbation approaches to identify probable protonation states of Na+- and K+-coordinating residues in E1P and E2P conformations of Na+/K+-ATPase…

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Computational and Experimental Evaluation of Designed β-Cap Hairpins Using Molecular Simulations and Kinetic Network Models.

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Molecular simulation has been used to model the detailed folding properties of peptides, yet prospective computational peptide design by such approaches remains challenging and nontrivial. To test the accuracy of simulation-based hairpin design, we characterized the folding properties of a series of so-called β-cap hairpin peptides designed to mimic a conserved hairpin of LapD, a bacterial intracellular signaling protein, both experimentally by NMR spectroscopy and computationally by implicit-…

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Precisely tuneable energy transfer system using peptoid helix-based molecular scaffold.

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The energy flow during natural photosynthesis is controlled by maintaining the spatial arrangement of pigments, employing helices as scaffolds. In this study, we have developed porphyrin-peptoid (pigment-helix) conjugates (PPCs) that can modulate the donor-acceptor energy transfer efficiency with exceptional precision by controlling the relative distance and orientation of the two pigments. Five donor-acceptor molecular dyads were constructed using zinc porphyrin and free base porphyrin (Zn(i …

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Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms.

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The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these is Streptococcus mutans, the causative agent of dental caries, the most prevalent childhood disease. Carolacton has remarkably specific activity against S. mutans, causing acid-mediated cell death during biofilm formation; however, its complex structure limits its utility. Herein, we report the diverted total synthesis and biological evaluation of a rationally designed library of simplified ana…

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