Understanding the role of negative charge in the scaffold of an artificial enzyme for CO hydrogenation on catalysis.

We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [Rh(PNP)]. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere.

Classifying metal-binding sites with neural networks.

To advance our ability to predict impacts of the protein scaffold on catalysis, robust classification schemes to define features of proteins that will influence reactivity are needed. One of these features is a protein's metal-binding ability, as metals are critical to catalytic conversion by metalloenzymes. As a step toward realizing this goal, we used convolutional neural networks (CNNs) to enable the classification of a metal cofactor binding pocket within a protein scaffold.

Mechanistic investigation of SARS-CoV-2 main protease to accelerate design of covalent inhibitors.

Targeted covalent inhibition represents one possible strategy to block the function of SARS-CoV-2 Main Protease (M), an enzyme that plays a critical role in the replication of the novel SARS-CoV-2. Toward the design of covalent inhibitors, we built a covalent inhibitor dataset using deep learning models followed by high throughput virtual screening of these candidates against M. Two top-ranking inhibitors were selected for mechanistic investigations-one with an activated ester warhead that has a piperazine core and the other with an acrylamide warhead.

sequencing and native mass spectrometry revealed hetero-association of dirigent protein homologs and potential interacting proteins in × .

The discovery of dirigent proteins (DPs) and their functions in plant phenol biochemistry was made over two decades ago with × Stereo-selective, DP-guided, monolignol-derived radical coupling was then reported to afford the optically active lignan, (+)-pinoresinol from coniferyl alcohol, provided one-electron oxidase/oxidant capacity was present. It later became evident that DPs have several distinct sub-families, presumably with different functions. Some known DPs require other essential enzymes/proteins ( oxidases) for their functions.

A protein scaffold enables hydrogen evolution for a Ni-bisdiphosphine complex.

An artificial metalloenzyme acting as a functional biomimic of hydrogenase enzymes was activated by assembly covalent attachment of the molecular complex, [Ni(PNP)], within a structured protein scaffold. Electrocatalytic H production was observed from pH 3.0 to 10.

Discovery of a Natural Product That Binds to the Protein Rv1466 Using Native Mass Spectrometry.

Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound's cellular activity.

Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state.

Encephalitozoon cuniculi is a unicellular, obligate intracellular eukaryotic parasite in the Microsporidia family and one of the agents responsible for microsporidosis infections in humans. Like most Microsporidia, the genome of E. cuniculi is markedly reduced and the organism contains mitochondria-like organelles called mitosomes instead of mitochondria.

Using Surface Amide Couplings to Assemble Photocathodes for Solar Fuel Production Applications.

A facile surface amide-coupling method was examined to attach dye and catalyst molecules to silatrane-decorated NiO electrodes. Using this method, electrodes with a push-pull dye were assembled and characterized by photoelectrochemistry and transient absorption spectroscopy. The dye-sensitized electrodes exhibited hole injection into NiO and good photoelectrochemical stability in water, highlighting the stability of the silatrane anchoring group and the amide linkage.

Visualizing biomolecular electrostatics in virtual reality with UnityMol-APBS.

Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson-Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages.

Evaluating the impacts of amino acids in the second and outer coordination spheres of Rh-bis(diphosphine) complexes for CO hydrogenation.

To explore the influence of a biologically inspired second and outer coordination sphere on Rh-bis(diphosphine) CO2 hydrogenation catalysts, a series of five complexes were prepared by varying the substituents on the pendant amine in the P(Et)2CH2NRCH2P(Et)2 ligands (PEtNRPEt), where R consists of methyl ester modified amino acids, including three neutral (glycine methyl ester (GlyOMe), leucine methyl ester (LeuOMe), and phenylalanine methyl ester (PheOMe)), one acidic (aspartic acid dimethyl ester (AspOMe)) and one basic (histidine methyl ester (MeHisOMe)) amino acid esters. The turnover frequencies (TOFs) for CO2 hydrogenation for each of these complexes were compared to those of the non-amino acid containing [Rh(depp)2]+ (depp) and [Rh(PEtNMePEt)2]+ (NMe) complexes. Each complex is catalytically active for CO2 hydrogenation to formate under mild conditions in THF.

Photosynthetic Microbial Fuel Cells.

This chapter presents the current state of research on bioelectrochemical systems that include phototrophic organisms. First, we describe what is known of how phototrophs transfer electrons from internal metabolism to external substrates. This includes efforts to understand both the source of electrons and transfer pathways within cells.

Hydrogen production from water using a bis(imino)pyridine molybdenum electrocatalyst.

In 5.0 M H2O/acetonitrile, [((Ph2PPr)PDI)MoO][PF6]2 produces H2 with 96% Faradaic efficiency at -2.5 V vs.