Calculating pKa of selected active site aminoacids in acetylcholinesterase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F11%3A00049967" target="_blank" >RIV/00216224:14740/11:00049967 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Calculating pKa of selected active site aminoacids in acetylcholinesterase

Popis výsledku v původním jazyce

Acetylcholinesterase (AChE) is an important enzyme participating in nerve signal transmission connected with Alzheimer disease and nerve agent poisoning. Initial molecular dynamics simulations using the Amber force field 03 have revealed a strong dependence of the dynamics on the protonation state of the AChE's active site. Simulations of the protonated AChE were much more stable than that of the deprotonated form where significant changes in the vicinity of the charged residues occurred. AChE's activesite contains three glutamic acid residues located close to each other (less than 8 A in the crystal structure). Using thermodynamic integration and the Amber force field 99SB, the pKa of these three glutamic acid residues was calculated. The calculatedpKa shift values appear to be overestimated and differ for forward and backward runs significantly. According to the results, AChE should have two of the three glutamate residues protonated.

Název v anglickém jazyce

Calculating pKa of selected active site aminoacids in acetylcholinesterase

Popis výsledku anglicky

Acetylcholinesterase (AChE) is an important enzyme participating in nerve signal transmission connected with Alzheimer disease and nerve agent poisoning. Initial molecular dynamics simulations using the Amber force field 03 have revealed a strong dependence of the dynamics on the protonation state of the AChE's active site. Simulations of the protonated AChE were much more stable than that of the deprotonated form where significant changes in the vicinity of the charged residues occurred. AChE's activesite contains three glutamic acid residues located close to each other (less than 8 A in the crystal structure). Using thermodynamic integration and the Amber force field 99SB, the pKa of these three glutamic acid residues was calculated. The calculatedpKa shift values appear to be overestimated and differ for forward and backward runs significantly. According to the results, AChE should have two of the three glutamate residues protonated.

Druh

O - Ostatní výsledky

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>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2011

Kód důvěrnosti údajů

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