| Name | Dr. Alberto Perez |
|---|---|
| Email hidden; Javascript is required. | |
| Organization | university of florida |
| Position | Faculty |
| Invited | No |
| Type | Oral |
| Topic | Physical Chemistry |
| Title | Targeting BET Proteins: Advances in Understanding Intrinsically Disordered Peptide Binding |
| Author(s) | Alberto Perez |
| Author Location(s) | university of florida |
| Abstract | Our team has developed MELD (Modeling Employing Limited Data), a novel approach for integrative structural biology to investigate the binding preferences of intrinsically disordered peptides that bind the ExtraTerminal domain (ET) of the BET family of proteins. BET proteins are critical targets in cancer, inflammation, and viral entry, and while inhibition strategies against the bromodomains have resulted in pan-inhibition, less is known about targeting the ET domain. MELD predicts accurate structures of the complex by combining chemical shift perturbation (CSP) data with molecular simulations, which is challenging due to the high level of flexibility in these complexes. We have also developed a fast and efficient assay based on AlphaFold to rank-order peptides by binding affinity. Our approach has allowed us to identify novel peptide inhibitors against BET-associated diseases, with the goal of achieving selectivity and specificity. |
