In our research, we use advanced computational chemistry and bioinformatics based tools such as homology modeling, protein-protein docking, virtual screening, molecular dynamics simulations and QM/MM methods, to develop new compounds that can be used as drug molecules, or to better understand the functions and interactions of proteins.
A large part of our work is directed towards cancer therapy, where we study a range of potential targets. In recent years, we have focused on a protein called IRE1 (inositol requiring enzyme 1) that is involved in the cellular response to / protection against stress, the unfolded protein response (UPR). Amongst other things, we explore how different proteins come together in a dynamic complex with IRE1, the ‘UPRosome’, and we have developed the first BBB penetrating inhibitor targeting the IRE1 kinase site. This compound has with great success been tested in preclinical experiments for treatment of the lethal and aggressive brain tumor glioblastoma multiforme (GBM).
Besides IRE1 and several other potential targets for cancer therapeutics, we also work with new methodology to better predict the structures of protein complexes, and machine learning in drug design. A part of our team is also conducting research on transcription factors and how these are able to recognize the ‘right’ sequence in DNA, and how DNA flexibility is governed by the specific order between nucleic acids.