Speaker
Description
Over the last decade, the combined development of accurate time-
resolved experimental techniques and advanced algorithms for
computer simulations has opened the possibility of investigating
biological mechanisms at atomic resolution with physics-based
models. In particular, combination of experimental information and
enhanced sampling techniques now allow the reconstruction 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 proteins. 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 folding
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.
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