Jiří Vondrášek: Bridging Domains and Disorder: Bioinformatics and Modeling of Protein–DNA and Protein–Protein Interactions

Proteins operate at the interface of order and disorder, with their functions often shaped by modular domains, flexible linkers, and intrinsically disordered regions. Our research combines bioinformatics, computational molecular biology, and molecular modeling to uncover the principles that govern this continuum.

 First, our investigations into transcription factors, a protein family central to gene regulation, show how extended sequence signals, DNA shape features, and disordered segments cooperate to fine-tune DNA recognition. These results, originating from work of my student in collaboration with our SIB partner, highlight the critical role of larger structural and sequence context in specificity and regulation.

Second, there will be discussed our long-term project on multi-domain proteins, with a focus on inter-domain linkers. These flexible elements serve as dynamic regulators of protein architecture, mediating structural communication, adaptability, and stability. By combining predictive bioinformatics with molecular simulations, we reveal how linkers and disordered regions are key design features in protein evolution.

Finally, the Integrated Database of Small Molecules (IDSM) will be introduced, a resource interlinking chemical space with biological interaction data from UniProt and Rhea. By connecting protein architecture with systems-level chemical biology, we aim to derive general rules for molecular recognition and function.