The Department of Biomedicine

BBB seminar: Knut Teigen

Computer simulations in structural biology – what is it good for?

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Knut Teigen
Department of Biomedicine, University of Bergen

Aromatic amino acid hydroxylases (AAHs) have been the subject of extensive research and experimental investigation for more than half a century. The elucidation of the 3D structure of tyrosine hydroxylase (TH) opened up a new era in the study of AAHs. The ability to access and study the information contained in the structure of TH made it possible to understand the vast amount of experimental data acquired throughout the preceding decades from a new perspective. Several structures of all three AAHs are now available, including those of complexes with cofactor, substrate, catecholamine inhibitors and substrate analogues. The structures of the ligand-bound forms of the enzymes open for rational discussions of structure-function-energetics relationships.

Computer simulations have been applied in our group to get a deeper understanding of the affinity and selectivity determinants for cofactor and substrate binding to AAHs. Molecular dynamics simulations provide us with a means for studying time-dependent properties of these systems at an atomic level of resolution. Information on the structural properties is provided directly. Accordingly, conformational changes can be investigated, as can interactions between molecules. However, the method has potentials beyond predicting the microscopic states of a system. Indirectly, through the use of theory from statistical mechanics, macroscopic thermodynamic properties can be derived. The prediction of bulk properties from relatively few atoms in a molecular dynamics simulation is an important aspect. Molecular dynamics is a possible approach when conditions or circumstances make attainment of experimental results problematic. Experimental techniques and molecular dynamics can be regarded as complementary tools in many cases, both in structural and thermodynamic studies.

Chair: Jeffrey Mc Kinney <jeffrey.mckinney@biomed.uib.no>, Department of Biomedicine