Structural Bioinformatics

Stanisław Dunin-Horkawicz

We focus on the development and application of bioinformatics tools to study the function of protein-based systems from an evolutionary perspective. This approach allows us to describe present-day systems in the context of the evolutionary events that shaped them, to define their unique and conserved features, and to propose testable hypotheses.

 

Protein Evolution

Detecting homology, or descent from a common ancestor, by sequence comparison is typically the first step in studying protein function and evolution. We have developed pLM-BLAST, a tool for identifying homologous regions between protein sequences. pLM-BLAST uses protein language models, deep neural networks trained on large amounts of protein sequence data, to make accurate predictions quickly. This method is actively developed and made available to the community through the MPI Bioinformatics Toolkit (https://toolkit.tuebingen.mpg.de/tools/plmblast). In our group, we use pLM-BLAST alongside other approaches to studying the evolution of protein-based systems. We are particularly interested in unraveling the deep ancestry of protein folds and the evolution of innate immunity and apoptosis systems.

Coiled-coil Structures

Protein coiled-coil domains comprise two or more alpha helices wrapped in regular bundles. Their inherent regularity allows coiled-coil structures to be described by parametric equations, enabling accurate quantification and in silico design of new structures with specified parameters. These properties make coiled coils an ideal model for studying the relationship between protein sequence, structure and function. In our group, we develop tools for detecting, classifying, and describing coiled coils in structures and sequences. We are interested in coiled-coil domains within prokaryotic signal transduction receptors, such as the HAMP domain, which link extracellular sensors to intracellular effectors. Our focus is on understanding how the dynamics of these domains contribute to their function.

Selected Publications

Winski, A., Ludwiczak, J., Orlowska, M., Madaj, R., Kaminski, K., and Dunin-Horkawicz, S. (2024) AlphaFold2 captures the conformational landscape of the HAMP signaling domain. epresentations from protein language models. Protein Sci. 33, e4846.   

Kaminski, K., Ludwiczak, J., Pawlicki, K., Alva, V., and Dunin-Horkawicz, S. (2023) pLM-BLAST: distant homology detection based on direct comparison of sequence representations from protein language models. Bioinformatics 39. 

Szczepaniak, K., Bukala, A., da Silva Neto, A.M., Ludwiczak, J., and Dunin-Horkawicz, S. (2021). A library of coiled-coil domains: from regular bundles to peculiar twists. Bioinformatics 36, 5368–5376.

Ludwiczak, J., Winski, A., Szczepaniak, K., Alva, V., and Dunin-Horkawicz, S. (2019). DeepCoil-a fast and accurate prediction of coiled-coil domains in protein sequences. Bioinformatics  35, 2790–2795.

Lupas, A., Bassler, J., and Dunin-Horkawicz, S. (2017). The Structure and Topology of α-Helical Coiled Coils. In Sub-Cellular Biochemistry, pp. 95–129.

Dunin-Horkawicz, S., Kopec, K.O., and Lupas, A.N. (2014). Prokaryotic ancestry of eukaryotic protein networks mediating innate immunity and apoptosis. J. Mol. Biol. 426, 1568–1582.

(see full publication list on Google Scholar)