Speaker: Frans Mulder, Associate Professor, Department of Chemistry, Aarhus University
Title: Probing and predicting the behavior of intrinsically disordered proteins by integrating NMR spectroscopy and computation
Abstract: I will focus on how we can utilize different NMR experimental observables to construct, validate, and improve models to understand protein behavior. I will discuss two topics: (1) NMR chemical shifts are exquisite probes of protein order and disorder, and are recognized proxies of local structure. Deviations from ‘random coil chemical shifts’ can, for example, be used to detect structured regions or motifs in intrinsically disorder in proteins. We have used NMR chemical shifts to assess the quality and bias in current protein disorder predictors and provide a ranking of these. Subsequently we built an even better one. (2) Hydrogen exchange (HX) is a very powerful way to probe protein structure and to deduce local stability and (un)folding kinetics. The slowing down of HX rates is typically due to hydrogen bond formation upon folding, although electrostatics also play a role. So far, the latter contribution has only been regarded qualitatively. I will show how we efficiently compute the electric potential in the vicinity of an intrinsically disordered protein, and how the thermodynamic concept of the electrochemical potential actually predicts the observed protection factors for the IDP alpha-synuclein.
For more information about this seminar and about joining in online, please contact Hyacinth Camillieri at email@example.com