All-atom simulations to studying metallodrugs/target interactions

Metallodrugs are extensively used to treat and diagnose distinct disease types. The unique physical?chemical proper-ties of metal ions offer tantalizing opportunities to tailor effec-tive scaffolds for selectively targeting specific biomolecules. Modern experimental techniques have collected a large body of structural data concerning the interactions of metallodrugs with their biomolecular targets, although being unable to exhaustively assess the molecular basis of their mechanism of action. In this scenario, the complementary use of accurate compu-tational methods allows uncovering the minutiae of metal-lodrugs/targets interactions and their underlying mechanism of action at an atomic-level of detail. This knowledge is increas-ingly perceived as an invaluable requirement to rationally devise novel and selective metallodrugs. Building on literature studies, selected largely from the last 2 years, this compen-dium encompasses a cross-section of the current role, ad-vances, and challenges met by computer simulations to decipher the mechanistic intricacies of prototypical metallodrugs.