Integrated experimental/computational approaches to characterize the systems formed by vanadium with proteins and enzymes

Decoding the interactions of transition metal complexes with proteins is still an open challenge in many fields, like biology and medicinal chemistry, or in the design of de novo enzymes, including artificial metalloenzymes. Instrumental techniques like X-ray crystallography or nuclear magnetic resonance can provide an atomistic description of the systems, although their application is often not trivial. In this review, we illustrate how the integrated approach based on spectrometric and spectroscopic techniques with multilevel molecular modelling allows characterization of metallodrug-protein adducts at the molecular level. A series of applications are described, focusing on potential vanadium drugs, with a final generalization to other metals. The data provide a major proof-of-concept of the power of coupled experimental and theoretical methods for the rational design of new metallodrugs as well as for guiding a large number of fields of bioinorganic chemistry.