Mechanism-Based Discovery of Novel Substrates of Haloalkane Dehalogenases using in Silico Screening

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F15%3A00081404" target="_blank" >RIV/00216224:14310/15:00081404 - isvavai.cz</a>

Výsledek na webu

<a href="http://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2015/01/jcim15.pdf" target="_blank" >http://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2015/01/jcim15.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/ci500486y" target="_blank" >10.1021/ci500486y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mechanism-Based Discovery of Novel Substrates of Haloalkane Dehalogenases using in Silico Screening

Popis výsledku v původním jazyce

The substrate specificity is a key feature of enzymes determining their applicability in biomaterials and biotechnologies. Experimental testing of activities with novel substrates is a time-consuming and inefficient process, typically resulting in many failures. Here, we present an experimentally validated in silico method for the discovery of novel substrates of enzymes with known reaction mechanism. The method was developed for a model system of biotechnologically relevant enzymes, haloalkane dehalogenases. Based on the parameterization of six different haloalkane dehalogenases with 30 halogenated substrates, mechanism-based geometric criteria for reactivity approximation were defined. These criteria were subsequently applied to the previously experimentally uncharacterized haloalkane dehalogenase DmmA. The enzyme was computationally screened against 42,000 compounds, yielding 548 structurally unique compounds as potential substrates.

Název v anglickém jazyce

Mechanism-Based Discovery of Novel Substrates of Haloalkane Dehalogenases using in Silico Screening

Popis výsledku anglicky

The substrate specificity is a key feature of enzymes determining their applicability in biomaterials and biotechnologies. Experimental testing of activities with novel substrates is a time-consuming and inefficient process, typically resulting in many failures. Here, we present an experimentally validated in silico method for the discovery of novel substrates of enzymes with known reaction mechanism. The method was developed for a model system of biotechnologically relevant enzymes, haloalkane dehalogenases. Based on the parameterization of six different haloalkane dehalogenases with 30 halogenated substrates, mechanism-based geometric criteria for reactivity approximation were defined. These criteria were subsequently applied to the previously experimentally uncharacterized haloalkane dehalogenase DmmA. The enzyme was computationally screened against 42,000 compounds, yielding 548 structurally unique compounds as potential substrates.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

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Svazek periodika

55

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

54-62

Kód UT WoS článku

000348619400005

EID výsledku v databázi Scopus

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