Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F11%3A33119772" target="_blank" >RIV/61989592:15310/11:33119772 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/11:00360708

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s10822-011-9413-5" target="_blank" >http://dx.doi.org/10.1007/s10822-011-9413-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10822-011-9413-5" target="_blank" >10.1007/s10822-011-9413-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors

Popis výsledku v původním jazyce

Abstract A semiempirical quantum mechanical PM6-DH2 method accurately covering the dispersion interaction and H-bonding was used to score fifteen structurally diverse CDK2 inhibitors. The geometries of all the complexes were taken from the X-ray structures and were reoptimised by the PM6-DH2 method in continuum water. The total scoring function was constructed as an estimate of the binding free energy, i.e., as a sum of the interaction enthalpy, interaction entropy and the corrections for the inhibitordesolvation and deformation energies. The applied scoring function contains a clear thermodynamical terms and does not involve any adjustable empirical parameter. The best correlations with the experimental inhibition constants (ln Ki) were found for bare interaction enthalpy (r2 = 0.87) and interaction enthalpy corrected for ligand desolvation and deformation energies (r2 = 0.77); when the entropic term was considered, however, the correlation becomes worse but still acceptable.

Název v anglickém jazyce

Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors

Popis výsledku anglicky

Abstract A semiempirical quantum mechanical PM6-DH2 method accurately covering the dispersion interaction and H-bonding was used to score fifteen structurally diverse CDK2 inhibitors. The geometries of all the complexes were taken from the X-ray structures and were reoptimised by the PM6-DH2 method in continuum water. The total scoring function was constructed as an estimate of the binding free energy, i.e., as a sum of the interaction enthalpy, interaction entropy and the corrections for the inhibitordesolvation and deformation energies. The applied scoring function contains a clear thermodynamical terms and does not involve any adjustable empirical parameter. The best correlations with the experimental inhibition constants (ln Ki) were found for bare interaction enthalpy (r2 = 0.87) and interaction enthalpy corrected for ligand desolvation and deformation energies (r2 = 0.77); when the entropic term was considered, however, the correlation becomes worse but still acceptable.

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)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

Journal of Computer-Aided Molecular Design

ISSN

0920-654X

e-ISSN

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Svazek periodika

25

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

223-235

Kód UT WoS článku

000288179000005

EID výsledku v databázi Scopus

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