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@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 and Michaela WIMMEROVÁ. Homology modeling of human intelectin-1. In DEMO, Gabriel and Michaela WIMMEROVÁ. \textit{XVI. Setkání biochemiků a molekulárních biologů}. 2014.
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