In silico prediction of protein misfolding and degradation
In order to function, most proteins require some conformational flexibility and are therefore only slightly thermodynamically stable in their native environment. Accordingly, as a result of stress conditions or mutations, proteins may lose their native conformation and misfold. Because misfolded proteins tend to form insoluble and toxic aggregates with other cell proteins, the accumulation of misfolded proteins represents a considerable threat to cells and the health of the organism. To cope with the potentially harmful misfolded proteins, cells have evolved an efficient protein quality control (PQC) network that functions to clear the cell of misfolded proteins. Typically, this relies on molecular chaperones that constantly surveil the intracellular space for non-native proteins. Upon encountering such misfolded proteins the chaperones may either refold them or guide them for degradation via the ubiquitin-proteasome system. Recently, we found that combining in silico saturation mutagenesis, structural modelling and biophysical calculations accurately predicts the abundance, rate of turnover, interaction and function of model proteins in vivo. This correlation allows us to utilize in silico biophysics to identify disease-linked SNPs in multiple human genetic disorders and points to the PQC network as a promising target for developing treatments for genetic disorders.
Invited by Xavier LE GOFF
>> Friday, March 30, 2018, 11 am - IGDR conference room (ground floor of Building 4 / Villejean Campus)
Seminar in English, free entry subject to availability