Role of metal ions in disordered biological systems: a modeling perspective

Ions have an essential role in many biological processes. In particular when the charge density is high (Mg, Ca, Zn) and when it changes according to microenvironmental conditions (Fe, Cu, Mn). Metal ions often interact with disordered proteins. The affinity is high enough to compete with structured proteins, but the structural and catalytic activity of the metal center is often out of control and, therefore, potentially dangerous for cells. In this talk I shall summarize this role with two examples. In the first example, we investigate the interactions between osteopontin and nucleic acids [1], describing the role of Mg in modulating protein association. In the second example, we apply a high-throughput modelling of Cu-amyloid beta complex in contact with dioxygen, with the aim at providing a tool to dissect the structural features that characterize dangerous catalysts in neurodegeneration [2,3]. The latter is a paradigmatic example where the oxidative pathway induced by sporadic copper catalysts triggers cell death. [1] http://dx.doi.org/10.3389/fchem.2018.00002 [2] http://dx.doi.org/10.1002/chem.201704654 [3] http://dx.doi.org/10.1021/acs.jpcb.8b03983