Quantum mechanical methods for the investigation of metalloproteins and related bioinorganic compounds

It is well known that transition metal ions are often bound to proteins, conveying very specific functional properties. In fact, metalloproteins play crucial biological roles in the transport and activation of small molecules such as H2, O2, and N2, as well as in several other biochemical processes. However, even if the presence of transition metals in the active site of proteins allows a very rich biochemistry, the experimental disclosure of structure-activity relationships in metalloproteins is generally difficult exactly because of the presence of transition metals, which are intrinsically characterized by a very versatile and often elusive chemistry. For this reason, computational methods are becoming very popular tools in the characterization of metalloproteins. In particular, since computing power is becoming less and less expensive, due to the continuous technological development of CPUs, the computational tools suited to investigate metalloproteins are becoming more accessible and therefore more commonly used also in molecular biology and biochemistry laboratories. Here, we present the main procedures and computational methods based on quantum mechanics, which are commonly used to study the structural, electronic, and reactivity properties of metalloproteins and related bioinspired compounds, with a specific focus on the practical and technical aspects that must be generally tackled to properly study such biomolecular systems.