Analysing structure-function relationships with biosensors

Abstract.

Elucidating the nature of the relationship between the structure and function of biomolecules remains one of the major challenges in biology. Biomolecules are dynamic entities that possess a variety of structures, and their functions at the molecular, cellular and organismic levels are quite different. Since there is no single causal link between structure and function, the search should be for correlations rather than causal relations. Biosensor instruments based on surface plasmon resonance are widely used for establishing correlations between the chemical structure of binding sites and their binding activity. Mutagenesis studies have shown that only a small percentage of the residues located in a binding site contribute to the binding energy. Since substitutions in residues located far away from the binding site are able to affect binding activity, this greatly complicates the rational design of proteins endowed with improved functions. However, biosensors can be used to determine and predict the influence of the chemical environment and of the structure of a ligand on binding kinetics.