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Nucleic acids and proteins are the key building blocks of life, yet many essential aspects of their relationship remain enigmatic. The aim of our research is to decipher the fundamental rules behind the interactions between nucleic acids and proteins in crowded environments, understand the impact these interactions have had in shaping life’s evolutionary history and study their role in present-day systems. The central hypothesis behind our research is that direct interactions between nucleic acids and proteins have contributed to the establishment of the universal genetic code and that, in turn, the code can be seen as a Rosetta stone for understanding RNA-protein interactions in general. A corollary of this hypothesis, which we are particularly interested in, is that mRNA coding sequences may be complementary to and bind in co-aligned fashion to their cognate proteins, especially if unstructured.
We use and develop different techniques of computational biology, including molecular dynamics simulations, free energy and entropy calculations and structural bioinformatics methods, in close conjunction with experiment. Moreover, we develop novel methods of what could best be described as physicochemical bioinformatics, an approach to representing, analyzing and comparing biological sequences as physicochemical objects, which they invariably are. By combining rigorous, atomistic description of individual biomolecules with the richness of modern-day proteomic and genomic datasets, we strive to discover new fundamental principles behind the organization of biological matter and explain essential biological phenomena from a quantitative, physicochemical perspective.
Bojan Zagrovic obtained an undergraduate degree in biochemistry from Harvard University and a PhD in biophysics from Stanford University, working with Vijay S. Pande. He was an EMBO postdoc with Wilfred F. van Gunsteren at ETH Zurich and a group leader and scientific director at Mediterranean Institute for Life Sciences in native Croatia. He joined Max Perutz Labs and University of Vienna in 2010.
We have shown that the nucleotide-density profiles of mRNA coding sequences closely match the nucleotide-affinity profiles of their cognate proteins, suggesting that mRNAs and the proteins that they encode may, in general, be physicochemically complementary to each other and bind in a co-aligned fashion, especially if unstructured.
We have recently developed VOLPES, a server for visualizing and comparing sequence profiles of different physicochemical properties of proteins and nucleic acids. VOLPES supports over 600 amino-acid and nucleotide property scales and enables multi-scale detection of patterns that may be inaccessible to standard methods of primary sequence analysis.
We have developed a parallel computational suite for the determination of conformational entropy change in biomolecular interactions from molecular dynamics simulation trajectories and have used it to demonstrate that intramolecular couplings provide a surprisingly constant contribution to the overall conformational entropy change in compact proteins.
RNA-protein interactions in an unstructured context.
Zagrovic, Bojan; Bartonek, Lukas; Polyansky, Anton A
Direct interplay between stereochemistry and conformational preferences in aminoacylated oligoribonucleotides.
Polyansky, Anton A; Kreuter, Mathias; Sutherland, John D; Zagrovic, Bojan
Frameshifting preserves key physicochemical properties of proteins.
Bartonek, Lukas; Braun, Daniel; Zagrovic, Bojan
European Research Council: Short, weakly interacting RNAligands for the development of high-concentration monoclonal antibody therapeutics
Austrian Science Fund: RNA-protein interactions in an unstructured context, 2018
Austrian Science Fund: 2’ vs. 3’ aminoacylation in biological translation
2016-2019: The Group Zagrovic participates in the special Doctoral Program "Integrative Structural Biology" reviewed and funded by the Austrian Science Fund FWF.
Awardee of a "Starting Independent Researcher Grant" from the European Research Council ERC
Project title: “Specific and global aspects of protein interactions”