[SY-H7] Multiscale modelling of intrinsically-disordered proteins
Proteins are often called the work-horse molecules of life because they are involved in almost any structure and activity in living systems. It has long been thought that proteins inherit their function from the secondary and tertiary structure in which they are folded. However, more and more evidence is appearing that show that also unfolded, intrinsically-disordered proteins (IDPs) play an important biological role, in both health and disease. In this work we focus on two of these biological roles, i.e., (i) in mediating transport through the nuclear pore complex (NPC) and (ii) in the formation of pathological protein aggregates in neurodegenerative diseases. IDPs are long chains of amino acids with conformations that are primarily dictated by the non-covalent interactions between the individual amino acids. Due to the large size of the protein complexes of interest, high-resolution (all-atom) molecular-dynamics simulations are restricted to study only a few IDPs. Here, we use a coarse-grained, one-bead-per-amino-acid model that is fine enough to capture the exact amino-acid sequence, but coarse enough to account for the collective interaction of hundreds of IDPs. In this presentation, recent results are presented on the collective behavior of IDPs in forming the selective permeability barrier of the NPC and on the phase-separation of pathological IDPs in the neurodegenerative disease ALS. For both studies the relation between amino-acid sequence and collective/aggregation behavior will be emphasized and discussed.