Homology modeling of human intelectin-1

a 2014

Homology modeling of human intelectin-1

HORSKÁ, Veronika, Gabriel DEMO, Ruben A. ABAGYAN a Michaela WIMMEROVÁ

Základní údaje

Originální název

Homology modeling of human intelectin-1

Autoři

HORSKÁ, Veronika (203 Česká republika, domácí), Gabriel DEMO (703 Slovensko, domácí), Ruben A. ABAGYAN (840 Spojené státy) a Michaela WIMMEROVÁ (203 Česká republika, garant, domácí)

Vydání

XVI. Setkání biochemiků a molekulárních biologů, 2014

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10600 1.6 Biological sciences

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14310/14:00077930

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

homology modeling intelectin-1

Změněno: 31. 12. 2014 17:38, Mgr. Gabriel Demo, Ph.D.

Anotace

V originále

Intelectin-1 (INTL-1) is an epithelial cell protein that is up-regulated in asthma, which is characterized by airway inflammation, mucus overproduction, airway hyperreactivity and peribronchial fibrosis. One possibility is that it participates in pathways of inflammation downstream of IL-13. Another possibility is that ITLN-1 is a component of airway mucus and contributes to pathologic mucus gel formation in disease. Because INTL-1 seems to be an effective therapeutic target and its structure is not known, homology modeling was used as an effective way to determine its 3D model structure for further virtual screening studies of potential inhibitors of INTL-1. The homology model of INTL-1 was built up in ICM software [6] according to suggested templates from CSI-BLAST, PSI-BLAST, HHMER, HHPRED and I-TASSER. To approve the stability of 3D model, 100 ns molecular dynamics (MD) simulations were performed. Based on the MD simulations a stable model was chosen to be able to provide further molecular docking calculations. A native ligand - galactofuranose in various conformations and anomer forms was used in semi-flexible docking for the potential binding site of INTL-1. The protein-ligand complexes after docking calculations were investigated with 30ns MD simulations to determine the stability of the protein-ligand complexes. The INTL-1 model with the best protein-ligand complex stability was chosen as an input model for virtual screening. The virtual screening for the INTL-1 model was performed with the usage of potential inhibitor libraries from Pubchem, that contain galactofuranose, D-xylose, D-ribose and deoxy-2-ribose residues. From each library the best-scored potential inhibitors were chosen. Further calculation will be necessary to assess the potential inhibitor binding during the MD simulation to confirm or disprove the stability of protein-inhibitor complexes.

Návaznosti

CZ.1.05/1.1.00/02.0068, interní kód MU

Název: CEITEC - středoevropský technologický institut (Akronym: CEITEC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC - středoevropský technologický institut, 1.1 Evropská centra excelence

Citovat

HORSKÁ, Veronika, Gabriel DEMO, Ruben A. ABAGYAN a Michaela WIMMEROVÁ. Homology modeling of human intelectin-1. In DEMO, Gabriel a Michaela WIMMEROVÁ. XVI. Setkání biochemiků a molekulárních biologů. 2014.

@proceedings{1214513,
   author = {Horská, Veronika and Demo, Gabriel and Abagyan, Ruben A. and Wimmerová, Michaela and Demo, Gabriel and Wimmerová, Michaela},
   booktitle = {XVI. Setkání biochemiků a molekulárních biologů},
   keywords = {homology modeling intelectin-1},
   language = {eng},
   title = {Homology modeling of human intelectin-1},
   year = {2014}
}

TY  - CONF
ID  - 1214513
AU  - Horská, Veronika - Demo, Gabriel - Abagyan, Ruben A. - Wimmerová, Michaela - Demo, Gabriel - Wimmerová, Michaela
PY  - 2014
TI  - Homology modeling of human intelectin-1
KW  - homology modeling intelectin-1
N2  - Intelectin-1 (INTL-1) is an epithelial cell protein that is up-regulated in asthma, which is characterized by airway inflammation, mucus overproduction, airway hyperreactivity and peribronchial fibrosis. One possibility is that it participates in pathways of inflammation downstream of IL-13. Another possibility is that ITLN-1 is a component of airway mucus and contributes to pathologic mucus gel formation in disease. Because INTL-1 seems to be an effective therapeutic target and its structure is not known, homology modeling was used as an effective way to determine its 3D model structure for further virtual screening studies of potential inhibitors of INTL-1. The homology model of INTL-1 was built up in ICM software [6] according to suggested templates from CSI-BLAST, PSI-BLAST, HHMER, HHPRED and I-TASSER. To approve the stability of 3D model, 100 ns molecular dynamics (MD) simulations were performed. Based on the MD simulations a stable model was chosen to be able to provide further molecular docking calculations. A native ligand - galactofuranose in various conformations and anomer forms was used in semi-flexible docking for the potential binding site of INTL-1. The protein-ligand complexes after docking calculations were investigated with 30ns MD simulations to determine the stability of the protein-ligand complexes. The INTL-1 model with the best protein-ligand complex stability was chosen as an input model for virtual screening. The virtual screening for the INTL-1 model was performed with the usage of potential inhibitor libraries from Pubchem, that contain galactofuranose, D-xylose, D-ribose and deoxy-2-ribose residues. From each library the best-scored potential inhibitors were chosen. Further calculation will be necessary to assess the potential inhibitor binding during the MD simulation to confirm or disprove the stability of protein-inhibitor complexes.
ER  -

HORSKÁ, Veronika, Gabriel DEMO, Ruben A. ABAGYAN a Michaela WIMMEROVÁ. Homology modeling of human intelectin-1. In DEMO, Gabriel a Michaela WIMMEROVÁ. \textit{XVI. Setkání biochemiků a molekulárních biologů}. 2014.

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