Non-globular proteins in the era of high accurate structure prediction

Abstract

Protein structure prediction has long been considered the “Holy Grail” of structural biology. The recent success of AlphaFold has ushered in a new era of highly accurate structure prediction, bringing to light the secrets hidden in the three-dimensional structures of globular proteins. However, a large proportion of the proteomes from all domains of life are rich in sequences that do not fold into regular structures, commonly known as non-globular proteins (NGPs). NGPs comprise intrinsically disordered regions, repeats, low-complexity sequences, aggregation-prone and phase-separating sequences, and are implicated in a range of age-related diseases. Their heterogeneous structural states and low sequence complexity challenge current experimental structure determination techniques and machine learning (ML) methods for structure prediction, making the molecular understanding of their sequence-structure-dynamics-function relationship difficult. The aim of this talk is to show the current efforts in the NGP field leaded by our lab BiocomputingUP (Prof. Silvio Tosatto Lab) at the University of Padova, as well as the community efforts consolidated in different consortia and European projects related to NGPs.