EmbrapaEmbrapaOur goal in this space is to overview the role of the local protein structure environment (which we will call here: nano-environment) in maintaining the functional purpose of different protein districts (defined as protein structure sites delimited by their functional objectives). Namely, we suggest that the local environment at each protein point and/or region reflects, not only its constitutional/structural role, but also its contribution to providing necessary and required characteristics for the functional objective that such particular site is supposed to have. For instance, protein–protein communication is executed through protein interfaces, and amino acid residues belonging to that site must have some specific characteristics which do not only differentiate them from the free surface residues, but also make possible that two very specific proteins may engage, bind and by doing so, perform their function. Similarly, enzyme function is normally related to activity of its catalytic site residues (CSRs). Obviously, these very peculiar residues are embedded in a very specific nano-environment (defined also by the contribution of CSR). Consequently, the enzyme function could be described in terms of characteristics of the CSRs and their surroundings. Based on the above considerations, and assuming that the local nano-environment is not only defining the protein district function, but it is also a concept for which we can design specific metrics to quantify it, and a specific set of properties to describe it, we studied the role of different descriptors and found that, some of them are of fundamental importance.