Quantum Mechanics-Based Scoring Rationalizes the Irreversible Inactivation of Parasitic Schistosoma mansoni Cysteine Peptidase by Vinyl Sulfone Inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33148129" target="_blank" >RIV/61989592:15310/13:33148129 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/13:00422118

Výsledek na webu

<a href="http://pubs.acs.org/doi/abs/10.1021/jp409604n" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/jp409604n</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jp409604n" target="_blank" >10.1021/jp409604n</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Quantum Mechanics-Based Scoring Rationalizes the Irreversible Inactivation of Parasitic Schistosoma mansoni Cysteine Peptidase by Vinyl Sulfone Inhibitors

Popis výsledku v původním jazyce

The quantum mechanics (QM)-based scoring function that we previously developed for the description of noncovalent binding in protein ligand complexes has been modified and extended to treat covalent binding of inhibitory ligands. The enhancements are (i)the description of the covalent bond breakage and formation using hybrid QM/semiempirical QM (QM/SQM) restrained optimizations and (ii) the addition of the new Delta G(cov)' term to the noncovalent score, describing the "free" energy difference betweenthe covalent and noncovalent complexes. This enhanced QM-based scoring function is applied to a series of 20 vinyl sulfone-based inhibitory compounds inactivating the cysteine peptidase cathepsin B1 of the Schistosoma mansoni parasite (SmCB1). The available X-ray structure of the SmCB1 in complex with a potent vinyl sulfone inhibitor K11017 is used as a template to build the other covalently bound complexes and to model the derived noncovalent complexes. We present the correlation of the

Název v anglickém jazyce

Quantum Mechanics-Based Scoring Rationalizes the Irreversible Inactivation of Parasitic Schistosoma mansoni Cysteine Peptidase by Vinyl Sulfone Inhibitors

Popis výsledku anglicky

The quantum mechanics (QM)-based scoring function that we previously developed for the description of noncovalent binding in protein ligand complexes has been modified and extended to treat covalent binding of inhibitory ligands. The enhancements are (i)the description of the covalent bond breakage and formation using hybrid QM/semiempirical QM (QM/SQM) restrained optimizations and (ii) the addition of the new Delta G(cov)' term to the noncovalent score, describing the "free" energy difference betweenthe covalent and noncovalent complexes. This enhanced QM-based scoring function is applied to a series of 20 vinyl sulfone-based inhibitory compounds inactivating the cysteine peptidase cathepsin B1 of the Schistosoma mansoni parasite (SmCB1). The available X-ray structure of the SmCB1 in complex with a potent vinyl sulfone inhibitor K11017 is used as a template to build the other covalently bound complexes and to model the derived noncovalent complexes. We present the correlation of the

Druh

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

CEP obor

CF - Fyzikální chemie a teoretická chemie

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)

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

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Svazek periodika

117

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

14973-14982

Kód UT WoS článku

000328101100010

EID výsledku v databázi Scopus

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