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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Modeling of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives by several conformational searching tools and
Mohammad Goodarzi1, Alina Bora, Ana Borota
1Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. mgoodarz@vub.ac.be
Abstract:
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.
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