Probing the structure–function relationship of proteins with molecular modeling

Proteins are complex biopolymers responsible for key functions in plant, microbial, fungal, and animal organisms. Due to the variability induced by the chemical composition of the 20 amino acid building blocks defining the primary sequence and the flexibility of the peptide bond, proteins are exhibiting various levels and degrees of structure. The secondary and tertiary structures are mainly driven by the interactions between the amino acid side chains and the solvent molecules to achieve a thermodynamically stable native state with a minimal free energy. Physiological or techno-functional higher levels of organization into quaternary structure or nonnative aggregates can be obtained when proteins are submitted to physical or chemical changes. Several models have been developed to account for the link between the molecular structure and arrangement of the protein and its potential functional properties. The latest advances in this field are described in this chapter and a series of structure–functionality prediction is also discussed.