GRID/BIOCUBE4mf to rank the influence of mutations on biological processes to design ad hoc mutants

One of the goals of protein engineering is to design mutants with improved biological profiles, i.e., broader specificity and elevated catalytic activity. Here, we propose a novel, fast and general protocol, based on new GRID/BIOCUBE4mf descriptors, to rank mutants for their ability to affect the pattern of interaction with the ligand, and thus their biological profile. The efficacy of the strategy is proven by establishing relationships between a new descriptor (SumΔn%) and Michaelis constants (K M) for a series of pentalenene synthase mutants.