Professor Kresten Lindorff-Larsen
Biomolecular Sciences
Structural Biology and NMR Laboratory, Linderstrom-Lang Centre for Protein Science, Univ. of Copenhagen
Copenhagen, Denmark

Monday, November 15, 2021
10:00 am (CT)
Zoom webinar recording

Abstract

Biological macromolecules are dynamic entities, and I will discuss methods and applications for how simulations and experiments can be used synergistically to study protein dynamics. Functional protein motions are often described as an exchange between a ground state structure and 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 proteins with extensive NMR data available as test systems, we have shown how enhanced sampling simulations can be used to capture accurately complex conformational changes in proteins, and I will briefly discuss such examples. Despite recent progress, one may still find that a simulation does not quantitatively match experiments. 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, and possible future approaches to include timescales of motion. I will also discuss how deviations between experiments and simulations may be used as starting point for data- driven optimization of force fields.