On the reliability of the corrected semiempirical quantum chemical method (PM6-DH2) for assigning the protonation states in HIV-1 protease/inhibitor complexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F11%3A00368013" target="_blank" >RIV/61388963:_____/11:00368013 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1135/cccc2011035" target="_blank" >http://dx.doi.org/10.1135/cccc2011035</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1135/cccc2011035" target="_blank" >10.1135/cccc2011035</a>

Jazyk výsledku

angličtina

Název v původním jazyce

On the reliability of the corrected semiempirical quantum chemical method (PM6-DH2) for assigning the protonation states in HIV-1 protease/inhibitor complexes

Popis výsledku v původním jazyce

A novel computational protocol for studying protonation in protein/ligand complexes is presented. We use a QM/MM approach in which the large QM part (the ligand and the active site) are treated using the corrected semiempirical method PM6-DH2, while theMM part (the rest of the protein and the surrounding solvent) are calculated using MM/GB method. This approach is applied to two model systems, the carboxylate pairs in HIV-1 protease/inhibitor complexes. The computationally more costly DFT optimizationsare performed for a smaller QM part as a check of the correctness. Proton transfer (PT) phenomena occur at both the PM6-D2 and DFT levels, which underlines the requirement for a QM approach. The barriers of PT are checked in model carboxylic acid pairsusing the highly accurate MP2 and CCSD(T) values. An important result of this study is the fine-tuning of the protocol which can be used in further applications; its limitations are also shown, pointing to future developments.

Název v anglickém jazyce

On the reliability of the corrected semiempirical quantum chemical method (PM6-DH2) for assigning the protonation states in HIV-1 protease/inhibitor complexes

Popis výsledku anglicky

A novel computational protocol for studying protonation in protein/ligand complexes is presented. We use a QM/MM approach in which the large QM part (the ligand and the active site) are treated using the corrected semiempirical method PM6-DH2, while theMM part (the rest of the protein and the surrounding solvent) are calculated using MM/GB method. This approach is applied to two model systems, the carboxylate pairs in HIV-1 protease/inhibitor complexes. The computationally more costly DFT optimizationsare performed for a smaller QM part as a check of the correctness. Proton transfer (PT) phenomena occur at both the PM6-D2 and DFT levels, which underlines the requirement for a QM approach. The barriers of PT are checked in model carboxylic acid pairsusing the highly accurate MP2 and CCSD(T) values. An important result of this study is the fine-tuning of the protocol which can be used in further applications; its limitations are also shown, pointing to future developments.

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

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

Collection of Czechoslovak Chemical Communications

ISSN

0010-0765

e-ISSN

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Svazek periodika

76

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

23

Strana od-do

457-479

Kód UT WoS článku

000290280100009

EID výsledku v databázi Scopus

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