Accelerating Peptide Discovery
Copyright 2012: CMD Bioscience. Computational Biotechnology. All rights reserved.
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Case 2: Caspase-3 peptide inhibitors
Caspase-3 is one of the key executioners of apoptosis, being responsible for the proteolytic cleavage of many key proteins. Caspase-3 is implicated in the apoptotic death of many mammalian cell types. Defects in apoptosis leads to some neurodegenerative disorders, ischemic injury, and cancer.
It is known Caspase-3 prefers a DXXD-like substrates. Here we applied CMDinventusSM to identify novel and optimizable peptide inhibitors for Caspase-3. Ac-DEVD-CHO bound crystal structure was used to define a binding surface. We next used CMDdesignSM, CMDmscoreSM, and CMDescoreSM work flows to screen virtual tetrapeptides and rank-order the top hits .
Peptide design predictions were synthesized and experimentally tested for inhibitory activity in a chromogenic protease assay.
