Kresten Lindorff-Larsen, Professor, Biomolecular Sciences, University of Copenhagen, Copenhagen, Denmark, will give a talk on "Biophysical experiments and biomolecular simulations: A perfect match?"

ABSTRACT

Biological macromolecules are dynamic entities and their ability to adopt alternative conformations can be central to their function. Examples include motions that underlie regulation or ligand binding, membrane proteins that act as efficient and selective transporters across biological membranes, or intrinsically disordered proteins that can adopt their shape to binding partners. I will discuss methods and applications for how simulations and experiments can be used synergistically to study protein and RNA dynamics.

Functional protein motions are often described as an exchange between a dominant, ground state structure and one or more minor states. The structural and biophysical properties of these transiently and sparsely populated states are, however, difficult to study, and an atomic-level description of those states is challenging. Using soluble protein and protein complexes with extensive NMR data available as a test system, we have shown how enhanced sampling simulations can be used to capture accurately complex conformational changes in proteins, and I will discuss such examples.

Despite recent progress, one may still find that a simulation does not match quantitatively experimental measurements. Then, experiments and simulations may be combined in a very direct fashion to provide a description of the molecular motions that combines the details of atomic simulations with the accuracy afforded by experiments. The resulting conformational ensembles may provide novel insight into biomolecular systems that are not obtainable by simulations of experiments alone. I will discuss how this may be achieved, and give examples of the application of such approaches using both NMR and small-angle scattering experiments to describe both proteins and RNA.