Shaila Ahmed and Raghu Prasad Rao Metpally and Sreedhara Sangadala and Boojala Vijay B Reddy
Computational Design of Inhibitory Agents of BMPNoggin Interaction to Promote Osteogenesis
329 - 333
2009
3
10
International Journal of Biomedical and Biological Engineering
https://publications.waset.org/pdf/1665
https://publications.waset.org/vol/34
World Academy of Science, Engineering and Technology
Bone growth factors, such as Bone Morphogenic
Protein2 (BMP2) 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 BMP2 by binding to BMP. Preventing
the BMP2noggin interaction will help increase the free
concentration of BMP2 and therefore should enhance its efficacy to
induce bone formation. The work presented here involves
computational design of novel small molecule inhibitory agents of BMP2noggin interaction, based on our current understanding of
BMP2, and its known putative ligands (receptors and antagonists). A
successful acquisition of such an inhibitory agent of BMP2noggin interaction would allow clinicians to reduce the dose required of
BMP2 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 BMPnoggin interaction with a high specificity.
Open Science Index 34, 2009