AlphaDesign: a de novo protein design framework based on AlphaFold

Title data

Jendrusch, Michael A. ; Yang, Alessio L. J. ; Cacace, Elisabetta ; Bobonis, Jacob ; Voogdt, Carlos G. P. ; Kaspar, Sarah ; Schweimer, Kristian ; Perez-Borrajero, Cecilia ; Lapouge, Karine ; Scheurich, Jacob ; Remans, Kim ; Hennig, Janosch ; Typas, Athanasios ; Korbel, Jan O. ; Sadiq, S. Kashif:
AlphaDesign: a de novo protein design framework based on AlphaFold.
In: Molecular Systems Biology. (2025) .
ISSN 1744-4292
DOI: https://doi.org/10.1038/s44320-025-00119-z

Official URL:

Abstract in another language

De novo protein design is of fundamental interest to synthetic biology, with a plethora of computational methods of various degrees of generality developed in recent years. Here, we introduce AlphaDesign, a hallucination-based computational framework for de novo protein design developed with maximum generality and usability in mind, which combines AlphaFold with autoregressive diffusion models to enable rapid generation and computational validation of proteins with controllable interactions, conformations and oligomeric state without the requirement for class-dependent model re-training or fine-tuning. We apply our framework to design and systematically validate in vivo active inhibitors of a family of bacterial phage defense systems with toxic effectors called retrons, paving the way towards efficient, rational design of novel proteins as biologics.

Further data

Item Type:	Article in a journal
Refereed:	Yes
Institutions of the University:	Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry IV - Biophysical Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry IV - Biophysical Chemistry > Chair Biochemistry IV - Biophysical Chemistry - Univ.-Prof. Dr. Janosch Hennig Research Institutions > Central research institutes > Nordbayerisches Zentrum für NMR-Spektroskopie - NMR-Zentrum
Result of work at the UBT:	Yes
DDC Subjects:	500 Science > 500 Natural sciences 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology
Date Deposited:	26 Jun 2025 05:27
Last Modified:	26 Jun 2025 05:27
URI:	https://eref.uni-bayreuth.de/id/eprint/93991