Increasing Affinity of Interferon-gamma Receptor 1 to Interferon-gamma by Computer-Aided Design

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F13%3A00420825" target="_blank" >RIV/86652036:_____/13:00420825 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1155/2013/752514" target="_blank" >http://dx.doi.org/10.1155/2013/752514</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1155/2013/752514" target="_blank" >10.1155/2013/752514</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Increasing Affinity of Interferon-gamma Receptor 1 to Interferon-gamma by Computer-Aided Design

Popis výsledku v původním jazyce

We describe a computer-based protocol to design protein mutations increasing binding affinity between ligand and its receptor. The method was applied to mutate interferon-gamma receptor 1 (IFN-gamma-Rx) to increase its affinity to natural ligand IFN-gamma, protein important for innate immunity. We analyzed all four available crystal structures of the IFN-gamma-Rx/IFN-gamma complex to identify 40 receptor residues forming the interface with IFN-gamma. For these 40 residues, we performed computational mutation analysis by substituting each of the interface receptor residues by the remaining standard amino acids. The corresponding changes of the free energy were calculated by a protocol consisting of FoldX and molecular dynamics calculations. Based on thecomputed changes of the free energy and on sequence conservation criteria obtained by the analysis of 32 receptor sequences from 19 different species, we selected 14 receptor variants predicted to increase the receptor affinity to IFN-ga

Název v anglickém jazyce

Increasing Affinity of Interferon-gamma Receptor 1 to Interferon-gamma by Computer-Aided Design

Popis výsledku anglicky

We describe a computer-based protocol to design protein mutations increasing binding affinity between ligand and its receptor. The method was applied to mutate interferon-gamma receptor 1 (IFN-gamma-Rx) to increase its affinity to natural ligand IFN-gamma, protein important for innate immunity. We analyzed all four available crystal structures of the IFN-gamma-Rx/IFN-gamma complex to identify 40 receptor residues forming the interface with IFN-gamma. For these 40 residues, we performed computational mutation analysis by substituting each of the interface receptor residues by the remaining standard amino acids. The corresponding changes of the free energy were calculated by a protocol consisting of FoldX and molecular dynamics calculations. Based on thecomputed changes of the free energy and on sequence conservation criteria obtained by the analysis of 32 receptor sequences from 19 different species, we selected 14 receptor variants predicted to increase the receptor affinity to IFN-ga

Druh

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

CEP obor

EI - Biotechnologie a bionika

OECD FORD obor

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Projekt

<a href="/cs/project/GAP305%2F10%2F2184" target="_blank" >GAP305/10/2184: Vztahy mezi strukturou a funkcí v proteinových interakcích</a><br>

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

BIOMED RESEARCH INTERNATIONAL

ISSN

2314-6133

e-ISSN

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Svazek periodika

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Číslo periodika v rámci svazku

752514

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

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Kód UT WoS článku

000325638500001

EID výsledku v databázi Scopus

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