| Title |
Computational peptide design for targeting homodimerization of BACH2 BTB domain and in vitro validations |
| Speaker |
Assoc. Prof. Ahmet Can Timuçin, PhD
Department of Molecular Biology and Genetics
Faculty of Engineering and Natural Sciences
Acıbadem University |
| Date |
February 12th, 2026
Thursday |
| Time |
15:00 (GMT+3) |
| Location |
ITU Informatics Institute
Room 413
|
Abstract
This talk will present the computational framework employed to identify a peptide capable of interfering with homodimerization of nuclear repressor BACH2 BTB domain, alongside wet lab validations. Activating master regulator of antioxidant response, the transcription factor NRF2 (Nuclear Factor Erythroid 2–Related Factor 2) through targeting its nuclear suppressor BACH2 represents an unexplored therapeutic strategy. Furthermore, the established role of BACH2 in tumor immunosuppression underscores the necessity of developing modulators against this repressor. To date, no peptide-based inhibitor targeting the BACH2 BTB domain has been reported. Therefore, this study aimed to identify a BACH2 inhibitory peptide using integrated computational and experimental approaches by characterizing its binding affinity and demonstrating its disruptive effect on homodimerization. As a preliminary step, a peptide library targeting the BACH2 BTB homodimerization interface was generated and screened via molecular docking to assess binding capacity at the dimerization surface. Subsequently, selected BACH2 BTB domain-peptide complexes were evaluated for binding stability through 500 ns molecular dynamics simulations, and trajectories were analyzed using MM-PBSA to estimate relative binding free energies. For experimental validation, selected peptides were ranked based on their dissociation constants to full-length BACH2 using supernatant depletion assays, with peptide 13 demonstrating higher affinity. Co-immunoprecipitation studies further revealed functionality of peptide 13 through disruption of BACH2 BTB domain homodimerization. Collectively, these findings established peptide 13 as a putative BACH2 negative regulator. Limitations of these findings and future directions on enhanced sampling-based peptide design towards intrinsically disordered regions will also be discussed.
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