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

Result code in 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>
Alternative codes found
RIV/61388963:_____/13:00422118
Result on the web
<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>

Result language
angličtina
Original language name
Quantum Mechanics-Based Scoring Rationalizes the Irreversible Inactivation of Parasitic Schistosoma mansoni Cysteine Peptidase by Vinyl Sulfone Inhibitors
Original language description
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
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CF - Physical chemistry and theoretical chemistry
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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