Speaker
Description
Over the last decade, the combined development of accurate time- resolved experimental tech- niques and advanced algorithms for computer simulations has opened the possibility of investigat- ing biological mechanisms at atomic resolution with physics-based models. In particular, combi- nation of experimental information and enhanced sampling techniques now allow the reconstruc- tion of the co- translational folding pathways of biologically relevant proteins, at an atomic level of resolution. These innovative computational technologies reveals the existence of non-native metastable states transiently appearing along the co-transcriptional folding process of such pro- teins. The lifetime of these intermediates is set by the amino- acid synthesis rate, hence is in the several second time scale. In this talk, we review the evidence indicating that these protein fold- ing intermediates play roles in post-translational regulation. We also discuss how the information encoded into protein folding pathways is being exploited in an entirely new generation of drugs capable of promoting the selective degradation of protein targets.
[1] G. Spagnolli et al., “Pharmacological inactivation of the prion protein by targeting a folding intermediate”, Communications Biology 4 (1), 6223–124 (2021). DOI:10.1038/s42003-020-01585-x. [2] E. Biasini and P. Faccioli “Functional, pathogenic, and pharmacological role of protein folding pathways”. Proteins. 2023; 1-9.
