Spectral decomposition of human BCL2 bonded to a PROTAC

Journal Article · Mon Dec 01 00:00:00 EST 2025 · The Journal of Chemical Physics

DOI:https://doi.org/10.1063/5.0288378· OSTI ID:3010628

Nauta, Wiestke ^[1]; De Graaf, Christophe ^[2]; Meul, Yentl ^[3]; Vissenberg, Kris ^[2]; Schoenaers, Sebastjen ^[2]; De Carvalho Vicente Da Cunha, Ana Or Ana Maria ^[4]

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1. University of Groningen
2. University of Antwerp, Belgium
3. University of Antwerp
4. ORNL

In this study, we have decomposed the linear infrared spectra and two-dimensional infrared spectroscopy of a VHL-recruiting Proteolysis-targeting chimera (PROTAC) complex with BCL-2 to understand the spectral signatures of this complex. Our findings show that both VHL and BCL-2 units have distinct spectral signatures that contribute to the total spectra in different regions. Furthermore, we observed that the interaction between VHL and BCL-2 within the PROTAC complex leads to unique spectral features, indicating a strong synergistic effect. Through detailed analysis, specific bands were identified that correspond to the vibrational modes of the individual components, as well as their interactive modes within the complex. This study provides valuable insight into the molecular interactions within the PROTAC complex, offering a deeper understanding of its structure and function. These insights could be pivotal in designing more efficient PROTACs for targeted protein degradation in therapeutic applications.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE
• Grant/Contract Number: AC05-00OR22725
• OSTI ID: 3010628
• Journal Information: The Journal of Chemical Physics, Journal Name: The Journal of Chemical Physics Journal Issue: 22 Vol. 163
• Country of Publication: United States
• Language: English