Nitriles

Bunch, Alan William

doi:10.1002/9783527620999.ch6h

Cited by 3 publications

(3 citation statements)

References 201 publications

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“…Here, our method was first verified by the de novo design towards the known aldehyde substrates of Gox0644 from the experiment (Supporting Information Table S1). For efficient generation of these substrates, six different types of fragments were used, namely the carbon atom, oxygen atom, chlorine atom, ethyl, benzene, and nitro group.…”

Section: Resultsmentioning

confidence: 99%

“…Many of their substrates are important intermediates in the synthesis of various pharmaceuticals and natural products. 21,22 Prior to the simulation, the catalysis mechanism and structure-function relationship of the two enzymes were carefully investigated. Crystal structures of Gox0644 (PDB code 3WBW) and nitrilase Nit6803 (PDB code 3WUY) determined in our previous studies were used.…”

Section: Validation On An Aldo-keto Reductase and A Nitrilasementioning

confidence: 99%

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Crius: A novel fragment‐based algorithm of de novo substrate prediction for enzymes

et al. 2018

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The study of enzyme substrate specificity is vital for developing potential applications of enzymes. However, the routine experimental procedures require lot of resources in the discovery of novel substrates. This article reports an in silico structure-based algorithm called Crius, which predicts substrates for enzyme. The results of this fragment-based algorithm show good agreements between the simulated and experimental substrate specificities, using a lipase from Candida antarctica (CALB), a nitrilase from Cyanobacterium syechocystis sp. PCC6803 (Nit6803), and an aldo-keto reductase from Gluconobacter oxydans (Gox0644). This opens new prospects of developing computer algorithms that can effectively predict substrates for an enzyme.

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Section: Resultsmentioning

confidence: 99%

Section: Validation On An Aldo-keto Reductase and A Nitrilasementioning

confidence: 99%

Crius: A novel fragment‐based algorithm of de novo substrate prediction for enzymes

et al. 2018

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“…To verify the utility of our method with different enzymes, another substrate-screening experiment using a distinct enzyme, nitrilase, was undertaken using THEMIS. Nitrilases catalyze the hydrolysis of organic nitriles to the corresponding carboxylic acids, some of which are important intermediates in the chemical synthesis of various products . A nitrilase from Cyanobacterium syechocystis sp.…”

Section: Resultsmentioning

confidence: 99%

A Semiautomated Structure-Based Method To Predict Substrates of Enzymes via Molecular Docking: A Case Study withCandida antarcticaLipase B

Yao

Zhang

Gao

et al. 2016

J. Chem. Inf. Model.

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The discovery of unique substrates is important for developing potential applications of enzymes. However, the experimental procedures for substrate identification are laborious, time-consuming, and expensive. Although in silico structure-based approaches show great promise, recent extensive studies have shown that these approaches remain a formidable challenge for current biocomputational methodologies. Here we present an open-source, extensible, and flexible software platform for predicting enzyme substrates called THEMIS, which performs in silico virtual screening for potential catalytic targets of an enzyme on the basis of the enzyme's catalysis mechanism. On the basis of a generalized transition state theory of enzyme catalysis, we introduce a modified docking procedure called "mechanism-based restricted docking" (MBRD) for novel substrate recognition from molecular docking. Comprising a series of utilities written in C/Python, THEMIS automatically executes parallel-computing MBRD tasks and evaluates the results with various molecular mechanics (MM) criteria such as energy, distance, angle, and dihedral angle to help identify desired substrates. Exhaustive sampling and statistical measures were used to improve the robustness and reproducibility of the method. We used Candida antarctica lipase B (CALB) as a test system to demonstrate the effectiveness of our computational prediction of (non)substrates. A novel MM score function for CALB substrate identification derived from the near-attack conformation was used to evaluate the possibility of chemical transformation. A highly positive rate of 93.4% was achieved from a CALB substrate library with 61 known substrates and 35 nonsubstrates, and the screening rate has reached 10 compounds/day (96 CPU cores, 100 samples/compound). The performance shows that the present method is perhaps the first reported scheme to meet the requirement for practical applicability to enzyme studies. An additional study was performed to validate the universality of our method. In this verification we employed two distinct enzymes, nitrilase Nit6803 and SDR Gox2181, where the correct rates of both enzymes exceeded 90%. The source code used will be released under the GNU General Public License (GPLv3) and will be free to download. We believe that the present method will provide new insights into enzyme research and accelerate the development of novel enzyme applications.

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The Behavior of a Fluorenyl-Based Host Compound in Four Organic Alkylnitrile Solvents

McFarlane,

Barton,

Hosten

2024

Crystal Growth & Design

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The host behavior of the compound 4,4′-(9-fluorenylidene)diphenol (H) bearing two rigid fluorenyl moieties and two alcohol functional groups was investigated in the presence of four alkylnitriles, namely acetonitrile (ACE), acrylonitrile (ACRY), propionitrile (PROP), and butyronitrile (BUT). Crystal growth of H from each of these nitriles furnished 1:1 host:guest inclusion complexes in each instance. Computational methods were employed in order to compare the low energy conformations of H with the guest-free molecular structure in the crystal obtained from single crystal X-ray diffraction analysis. Each of the complexes crystallized in the monoclinic crystal system and the centrosymmetric space group P21/n, and the host packing was isostructural in each case. The nitrile guest compounds experienced a classical (host)O–H···N(guest) hydrogen bond with the host molecule, the H···N, O···N, and ∠DHA parameters being 1.97, 2.772(3) Å, 159° (H·ACE), 1.94, 2.759(2) Å, 166° (H·ACRY), 1.91, 2.738(3) Å, 167° (H·PROP), and 1.95, 2.779(2) Å, 171° (H·BUT); this bond was thus significantly shorter in the PROP-containing inclusion compound than in the remaining three clathrates. The thermal stabilities of the four complexes were also examined together with Hirshfeld surface considerations. Finally, lattice energy calculations were carried out and the results of these compared with the relative thermal stabilities of the four complexes.

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Nitriles

Cited by 3 publications

References 201 publications

Crius: A novel fragment‐based algorithm of de novo substrate prediction for enzymes

Crius: A novel fragment‐based algorithm of de novo substrate prediction for enzymes

A Semiautomated Structure-Based Method To Predict Substrates of Enzymes via Molecular Docking: A Case Study withCandida antarcticaLipase B

The Behavior of a Fluorenyl-Based Host Compound in Four Organic Alkylnitrile Solvents

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