Abstract:
:Using ligand and receptor based virtual screening approaches we have identified potential virtual screening hits targeting type II dehydroquinase from Mycobacterium tuberculosis, an effective and validated anti-mycobacterial target. Initially, we applied a virtual screening workflow based on a combination of 2D structural fingerprints, 3D pharmacophore and molecular docking to identify compounds that rigidly match specific aspects of ligand bioactive conformation. Subsequently, the resulting compounds were ranked and prioritized using receptor interaction fingerprint based scoring and quantitative structure activity relationship model developed using already known actives. The virtual screening hits prioritized belong to several classes of molecular scaffolds with several available substitution positions that could allow chemical modification to enhance binding affinity. Finally, identified hits may be useful to a medicinal chemist or combinatorial chemist to pick up the new molecular starting points for medicinal chemistry optimization for the design of novel type II dehydroquinase inhibitors.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Kumar A,Siddiqi MI,Miertus Sdoi
10.1007/s00894-009-0595-xsubject
Has Abstractpub_date
2010-04-01 00:00:00pages
693-712issue
4eissn
1610-2940issn
0948-5023journal_volume
16pub_type
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