TY - JOUR
T1 - Modeling of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives by several conformational searching tools and molecular docking
AU - Goodarzi, Mohammad
AU - Bora, Alina
AU - Borota, Ana
AU - Funar-Timofei, Simona
AU - Avram, Sorin
AU - Heyden, Yvan Vander
PY - 2013/5/21
Y1 - 2013/5/21
N2 - Neutrophil elastase, a serine proteinase from the chymotrypsin family, has been the object of comprehensive experimental and theoretical studies to develop efficient human neutrophil elastase inhibitors. The serine protease has been linked to the pathology of a variety of inflammatory diseases, making it an attractive target for the development of anti-inflammatory compounds. In this work, we have built a common binding model of the 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives into the human neutrophil elastase binding site. This was accomplished through a comparative conformational analysis (using OMEGA, HYPERCHEM, and MOPAC software) of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one inhibitors followed by rigid and flexible molecular docking (by the FRED and GLIDE programs) into the target protein. We conclude that OMEGA software generates the most representative conformers to model the protein-ligand interactions.
AB - Neutrophil elastase, a serine proteinase from the chymotrypsin family, has been the object of comprehensive experimental and theoretical studies to develop efficient human neutrophil elastase inhibitors. The serine protease has been linked to the pathology of a variety of inflammatory diseases, making it an attractive target for the development of anti-inflammatory compounds. In this work, we have built a common binding model of the 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives into the human neutrophil elastase binding site. This was accomplished through a comparative conformational analysis (using OMEGA, HYPERCHEM, and MOPAC software) of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one inhibitors followed by rigid and flexible molecular docking (by the FRED and GLIDE programs) into the target protein. We conclude that OMEGA software generates the most representative conformers to model the protein-ligand interactions.
KW - Benzoxazinone derivative
KW - Biologically active conformation
KW - Conformational analysis
KW - Human neutrophil elastase inhibitor
KW - Molecular docking
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U2 - 10.2174/1381612811319120007
DO - 10.2174/1381612811319120007
M3 - Article
C2 - 23016845
AN - SCOPUS:84877794682
SN - 1381-6128
VL - 19
SP - 2194
EP - 2203
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 12
ER -