Studier av molekylära interaktioner - från proteinfunktion och reglering av biologiska processer till design av läkemedel
Tidsperiod: 2014-01-01 till 2016-12-31
Budget: 2 250 000 SEK
AIMS: To obtain fundamental insights into the molecular basis of protein interactions with metal ions, ligands and other proteins, ultimately related to the chemical principles of regulation of biological processes and drug action. STRATEGY: To use SPR-biosensor technology for time-resolved interaction analysis, complemented by other biophysical techniques, structural and computational methods. The experiments will provide kinetic, mechanistic, thermodynamic and chemodynamic details of selected model systems. The work is divided into three thematic areas: A. Regulation of protein function via binding of metal ions, B. Protein dynamics, ligand binding and ion channel function, and C. Thermodynamics of protein-ligand interactions. EXPERIMENTS: Analysis of interactions between thrombin and Na+, and the impact on inhibitor binding, between calmodulin, Ca2+ and CaMII kinase, and between CRP, Ca2+ and cell membranes. Analysis of the conformational dynamics of ion channels and their regulation by ligands, and of the thermodynamics of protein-metal ion and ligand interactions. PREVIOUS RESULTS: We have established biosensor technology for detailed studies of molecular interactions and revealed structure, kinetic, thermodynamic and mechanistic relationships. It has had a significant impact on enzymology and drug design. SIGNIFICANCE: The project will contribute novel insights on molecular recognition and detailed information for several important systems.