Quantum Mechanical Scoring: Structural and Energetic Insights into Cyclin-Dependent Kinase 2 Inhibition by Pyrazolo[1,5-a]pyrimidines

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33147917" target="_blank" >RIV/61989592:15310/13:33147917 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/13:00394206 RIV/00159816:_____/13:00060664 RIV/00216224:14310/13:00067855 RIV/00209805:_____/13:#0000438
Result on the web
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DOI - Digital Object Identifier
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Result language
angličtina
Original language name
Quantum Mechanical Scoring: Structural and Energetic Insights into Cyclin-Dependent Kinase 2 Inhibition by Pyrazolo[1,5-a]pyrimidines
Original language description
A quantum mechanics (QM)-based scoring function has been applied to complexes of cyclin-dependent kinase 2 (CDK2) and thirty-one pyrazolo[1,5-a]pyrimidine-based inhibitors and their bioisosteres. A hybrid three-layer QM/MM setup (DFT-D/PM6-D3H4X/AMBER ingeneralized Born solvent) was used here for the first time as an extension of our previous full QM and SQM/MM (SQM means semiempirical QM) approaches. Two approaches to obtain the structures of the CDK2/inhibitor complexes were examined: i) building themodifications from one X-ray structure available coupled with a conformational search and ii) docking the compounds into CDK2. The QM-based scoring entailed a QM/SQM/MM optimization followed by calculations of the binding scores which were subsequentlycorrelated with the experimental binding free energies. The correlation for the building protocol was good (r(2) = 0.64, predictive index = 0.81), whereas the docking approach failed. A decomposition of the interaction energies to ligand
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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