Anna Linusson Lab

Our research is directed towards fundamental aspects of interactions of small-molecular ligands with proteins, using both experimental and computational techniques. The research is performed within pharmaceutical relevant projects to contribute to the discovery of new molecules against for example sleeping sickness disease, malaria and dengue fever.

The association between molecules (ligands) and macromolecules plays a key role in biological processes. The research aims to understand how the geometry and energy of protein-ligand interactions influence the molecular recognition. The research combines computational chemistry with organic synthesis, kinetic and thermodynamic studies, structure determination and biological evaluation. The research in the group is focused on two classes of proteins, metacaspases and acetylcholinesterases (AChE). Metacaspases controls fundamental biological processes, such as aging and cell proliferation, differentiation and death in all kingdoms of life except animals. AChE terminates synaptic transmission through hydrolysis of acetylcholine.

Specific research aims in the lab include:

• Exploration of the geometry and binding energy of non-covalent interactions in AChE-ligand complexes by organic synthesis, X-ray crystallography, kinetic and thermodynamic studies to gain knowledge of molecular recognition
• In depth computational studies of aromatic and weak hydrogen bond interactions in AChE-ligand complexes by molecular mechanics and quantum chemistry to develop methods by which we can quantify binding energy components and estimate free energy of binding
• Design and synthesise novel AChE ligands of medical interest by using the developed computational and experimental methods and the gained understanding of the system
• Development of high-selectivity metacaspase-specific chemical probes by computer-based design, organic synthesis, X-ray crystallography, and biochemical and biological evaluations
• Exploration of the activation mechanism of metacaspases by computational chemistry, organic synthesis, X-ray crystallography and kinetic and thermodynamic studies.
• Design and develop synthetic active ingredients to prevent infectious diseases spread by mosquitos and other vectors, focusing on dengue, sleeping sickness disease, yellow fever and malaria