Structural Basis of the Interaction of Cyclin-Dependent Kinase 2 with Roscovitine and Its Analogues Having Bioisosteric Central Heterocycles
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00476134" target="_blank" >RIV/61388963:_____/17:00476134 - isvavai.cz</a>
Alternative codes found
RIV/61389030:_____/17:00476134 RIV/61989592:15310/17:73584529 RIV/00159816:_____/17:00066873 RIV/00216224:14310/17:00097036
Result on the web
<a href="http://dx.doi.org/10.1002/cphc.201601319" target="_blank" >http://dx.doi.org/10.1002/cphc.201601319</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cphc.201601319" target="_blank" >10.1002/cphc.201601319</a>
Alternative languages
Result language
angličtina
Original language name
Structural Basis of the Interaction of Cyclin-Dependent Kinase 2 with Roscovitine and Its Analogues Having Bioisosteric Central Heterocycles
Original language description
The structural basis for the interaction of roscovitine and analogues containing 13 different bioisosteric central heterocycles with the enzyme cyclin-dependent kinase 2 (CDK2) is elucidated. Although all the central scaffolds are very similar to the purine core of roscovitine, the experimentally determined IC50 values of the inhibitors span three orders of magnitude. By using an extensive computational chemistry approach, the affinities of the inhibitors to CDK2 are determined as calculated binding scores of complexes of the inhibitors with the protein. The interactions of the inhibitors with CDK2 are computationally described by using a hybrid quantum mechanics/semi-em-pirical quantum mechanics method (QM/SQM), which combines the DFT-D method for the QM part and the PM6-D3H4X method for the SQM part. The solvent effect is described by the COSMO implicit solvation model at the SQM level for the whole system. The contributions of the scaffolds and the individual substituents, quantified and evaluated in relation to conformations of optimized protein-inhibitor complexes, are found not to be simply additive. The inhibitory activity of the selected candidates, including two newly prepared compounds, is tested against CDK2. The results of the calculations are in close agreement with the experimental data.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
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)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ChemPhysChem
ISSN
1439-4235
e-ISSN
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Volume of the periodical
18
Issue of the periodical within the volume
7
Country of publishing house
DE - GERMANY
Number of pages
11
Pages from-to
785-795
UT code for WoS article
000402711100009
EID of the result in the Scopus database
2-s2.0-85013293315