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Designed dynamic proteins

Group members:

dr. Ajasja Ljubetič, PI

Eva Rajh, PhD student

Tadej Satler, PhD student

Liza Ulčakar, PhD student

Alina Konstantinova, PhD student

Nej Bizjak, Diploma’s student

David Krisper, Master’s student

Neža Ribnikar, Master's student

Open Postdoc position (link)

We focus on the design and study of de novo designed dynamic protein assemblies, with a particular emphasis on coiled coil structures. Coiled coils are formed by two or more alpha helices that are wound around each other in a specific way, and they play important roles in many biological processes.

During my postdoc in the Baker Lab we have designed a de novo random walker, that uses coiled coils as feet. We are now making the feet rigid in order to enable biased motion and active walking. We are also exploring future applications of this random walker scaffold in order to build useful protein robots. 

We use the Rosetta software to rigidly fuse coiled coils to de novo designed proteins. We also employ state of the art deep learning methods, such as Alphafold2, RFDiffusion and Protein MPNN.  This allows us to get the best of both worlds: the binding versatility and orthogonality of coiled coils and the stability and shape variability of designed proteins. By exploring the potential of de novo designed proteins, we hope to make important contributions to the field of biotechnology.

Recent publications:

1) Design of in vivo self-assembling coiled-coil protein origami [IF:41]
, Ajasja, LAPENTA*, Fabio, GRADIŠAR, Helena, DROBNAK, Igor, AUPIČ, Jana, STRMŠEK, Žiga, LAINŠČEK, Duško, HAFNER BRATKOVIČ, Iva, MAJERLE, Andreja, KRIVEC, Nuša, BENČINA, Mojca, PISANSKI, Tomaž, ĆIRKOVIĆ-VELIČKOVIĆ, Tanja, ROUND, Adam R., CARAZO, José María, MELERO, Roberto, JERALA, Roman. 7 Nature biotechnology. Nov. 2017, vol. 35, no. 11, str. 1094-1101. ISSN 1087-0156, DOI: 10.1038/nbt.3994.

2) A multiplexed bacterial two-hybrid for rapid characterization of protein-protein interactions and iterative protein design. [IF:16.6]
BOLDRIDGE*, W. Clifford, LJUBETIČ*#, Ajasja, KIM, Hwangbeom, LUBOCK, Nathan, SZILÁGYI, Dániel, LEE, Jonathan, BRODNIK, Andrej, JERALA#, Roman, KOSURI#, Sriram. Nature communications. 2023, 4636, vol. 14 10.1038/s41467-023-38697-x.

3) Interpreting neural networks for biological sequences by learning stochastic masks [IF: 25.9]
LINDER, Johannes, LA FLEUR, Alyssa, CHEN, Zibo, LJUBETIČ, Ajasja, BAKER, David C., KANNAN, Sreeram, SEELIG, Georg. Nature machine intelligence. 2022, vol. 4, str. 41-54, ilustr. ISSN 2522-5839, DOI: 10.1038/s42256-021-00428-6

4) Advances in design of protein folds and assemblies. [IF: 7.6]
, GRADIŠAR, Helena, JERALA, Roman. Current opinion in chemical biology, ISSN 1367-5931, Oct. 2017, vol. 40, str. 65.  doi: 10.1016/j.cbpa.2017.06.020.

5) Designed folding pathway of modular coiled-coil-based proteins [IF 17.7]
AUPIČ, Jana, STRMŠEK, Žiga, LAPENTA, Fabio, PAHOVNIK, David, PISANSKI, Tomaž, DROBNAK, Igor, LJUBETIČ, Ajasja, JERALA, Roman. Nature communications. 2021, vol. 12, str. 1-12, ilustr. ISSN 2041-1723, DOI: 10.1038/s41467-021-21185-5.

Running projects:

J1-4406 CC-Trigger: izpodrivanje proteinskih obvitih vijačnic s pomočjo oprimkov omogoča kinetični nadzor proteinskih sestavov in napredne naprave z več stanji, 2022-2025, Cofunded by Slovenian Research and Innovation Agency (ARIS)

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