Research group Samuel Flores' research group
What do we do once the world's genomes have been sequenced? There is still the question of what these molecules look like once they are transcribed into RNA (we work on this) and from there translated to protein (where Google's AlphaFold has made great progress) and what they do in the cell.
Group description
Determining the impact of mutations on Protein-protein interaction energies
I have written a few papers on predicting the change in protein-protein interaction energy (ΔΔG) resulting from mutations. I want to develop the capability to increase affinity in silico, and as a second priority, alter specificity. Recently, I have developed a method which asks the user for a the Protein Data Bank (PDB) ID of a protein-protein complex, the chains in each of two interacting subunits, and a mutation to test. It not only computes ΔΔG using that structure (using the FoldX potential) but also searches the PDB for additional, sufficiently-similar structures on which to repeat the calculation. It then averages over the results of all such calculation, thus improving precision and (importantly) positive predictive value -- the fraction of mutations which are predicted to improve affinity, which successfully do so. You can try this out on our easy to use web server, http://biodesign.scilifelab.se/.
Toward designing RNA-complexes for nanotechnology
The flexibility of large RNAs presents a significant challenge to understanding large complexes such as the ribosome, and to designing complexes for nanotechnology. Previously, experiments have been performed which has successfully folded tRNA and the P4/P6 domain of the Group I Intron, threaded the Azoarcus Group I Intron, explained the role of disease associated mutations in telomerase, and modeled all-atoms trajectories of ribosomal translocation. The latter drove development of very fast morphing and low-resolution (e.g. cryoem) density map fitting methods. We also written about GTP hydrolysis on EF-G and ribosomal frameshifting. Current projects include deep learning for RNA structure prediction, and viral DNA genome packaging.
Current MS students (Spring 2022):
Kaouther Harbi
Floyd Jaggy
Emilio Skarwan
Group members
Group managers
Samuel Flores
Director for Research School in Bioinformatics
Members
Gabriele Pozzati
PhD student
