The Department of Biomedicine

BBB seminar: Lars Skjærven

Bringing structural biology data to life with computer simulations – research and experiences from EMBL

Lars Skjærven
Department of Biomedicine, University of Bergen

Biomolecules such as proteins and nucleic acids are intrinsically flexible molecules with the ability to adapt their conformation in response to environmental stimuli such as ligand binding. Such conformational switching is often intimately coupled to their specific biochemical activities, and facilitates the modulation of the vast number of biological processes in living organisms. This structure-function relationship has motivated the development of computational tools to characterize internal protein motions, as well as to predict protein-ligand interactions. In this talk I will present the development and application of techniques of structural bioinformatics for (i) studying protein allostery and long-range interactions, and (ii) protein-ligand structure determination. We show with detailed molecular dynamics simulations key mechanisms along the functional cycle of GroEL-GroES – a molecular chaperone with allosteric regulation showing both positive and negative cooperativity. Our input to the development of new techniques for protein-ligand structure determination features a previously unexplored integration between molecular modeling and experimental data obtained from NMR with promising potential in structure-based drug design. This combination of theory and experimental data represents an important direction in understanding detailed molecular mechanisms, and resolving challenges in structural molecular biology that could not be solved by experimental techniques alone.

Chairperson: Aurora Martinez, Department of Biomedicine