WASET
	%0 Journal Article
	%A Shaila Ahmed and  Raghu Prasad Rao Metpally and  Sreedhara Sangadala and  Boojala Vijay B Reddy
	%D 2009
	%J International Journal of Biomedical and Biological Engineering
	%B World Academy of Science, Engineering and Technology
	%I Open Science Index 34, 2009
	%T Computational Design of Inhibitory Agents of BMP-Noggin Interaction to Promote Osteogenesis
	%U https://publications.waset.org/pdf/1665
	%V 34
	%X Bone growth factors, such as Bone Morphogenic
Protein-2 (BMP-2) have been approved by the FDA to replace grafting for some surgical interventions, but the high dose requirement limits its use in patients. Noggin, an extracellular protein, blocks the effect of BMP-2 by binding to BMP. Preventing
the BMP-2/noggin interaction will help increase the free
concentration of BMP-2 and therefore should enhance its efficacy to
induce bone formation. The work presented here involves
computational design of novel small molecule inhibitory agents of BMP-2/noggin interaction, based on our current understanding of
BMP-2, and its known putative ligands (receptors and antagonists). A
successful acquisition of such an inhibitory agent of BMP-2/noggin interaction would allow clinicians to reduce the dose required of
BMP-2 protein in clinical applications to promote osteogenesis. The
available crystal structures of the BMPs, its receptors, and the binding partner noggin were analyzed to identify the critical residues
involved in their interaction. In presenting this study, LUDI de novo design method was utilized to perform virtual screening of a large
number of compounds from a commercially available library against the binding sites of noggin to identify the lead chemical compounds
that could potentially block BMP-noggin interaction with a high specificity.
	%P 329 - 333