QM/MM Calculations Reveal the Different Nature of the Interaction of Two Carborane-Based Sulfamide Inhibitors of Human Carbonic Anhydrase II

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33148159" target="_blank" >RIV/61989592:15310/13:33148159 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/13:00424087 RIV/61388963:_____/13:00424087

Výsledek na webu

<a href="http://pubs.acs.org/doi/abs/10.1021/jp410216m" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/jp410216m</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jp410216m" target="_blank" >10.1021/jp410216m</a>

Jazyk výsledku

angličtina

Název v původním jazyce

QM/MM Calculations Reveal the Different Nature of the Interaction of Two Carborane-Based Sulfamide Inhibitors of Human Carbonic Anhydrase II

Popis výsledku v původním jazyce

The crystal structures of two novel carborane-sulfamide inhibitors in the complex with human carbonic anhydrase II (hCAII) have been studied using QM/MM calculations. Even though both complexes possess the strongly interacting sulfamide center dot centerdot center dot zinc ion motif, the calculations have revealed the different nature of binding of the carborane parts of the inhibitors. The neutral closo-carborane cage was bound to hCAII mainly via dispersion interactions and formed only very weak dihydrogen bonds. On the contrary, the monoanionic nido age interacted with the protein mainly via electrostatic interactions. It formed short and strong dihydrogen bonds (stabilization of up to 4.2 kcal/mol; H center dot center dot center dot H distances of1.7 angstrom) with the polar hydrogen of protein NH2 groups. This type of binding is unique among all of the classical organic and inorganic inhibitors of hCAII. Virtual glycine scanning allowed us to identify the amino-acid side chains,

Název v anglickém jazyce

QM/MM Calculations Reveal the Different Nature of the Interaction of Two Carborane-Based Sulfamide Inhibitors of Human Carbonic Anhydrase II

Popis výsledku anglicky

The crystal structures of two novel carborane-sulfamide inhibitors in the complex with human carbonic anhydrase II (hCAII) have been studied using QM/MM calculations. Even though both complexes possess the strongly interacting sulfamide center dot centerdot center dot zinc ion motif, the calculations have revealed the different nature of binding of the carborane parts of the inhibitors. The neutral closo-carborane cage was bound to hCAII mainly via dispersion interactions and formed only very weak dihydrogen bonds. On the contrary, the monoanionic nido age interacted with the protein mainly via electrostatic interactions. It formed short and strong dihydrogen bonds (stabilization of up to 4.2 kcal/mol; H center dot center dot center dot H distances of1.7 angstrom) with the polar hydrogen of protein NH2 groups. This type of binding is unique among all of the classical organic and inorganic inhibitors of hCAII. Virtual glycine scanning allowed us to identify the amino-acid side chains,

Druh

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

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

—

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

—

Svazek periodika

117

Číslo periodika v rámci svazku

50

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

16096-16104

Kód UT WoS článku

000328920600018

EID výsledku v databázi Scopus

—