Biomolecules rarely function in isolation, hence a thorough understanding of biological processes is dependent upon an examination of complexes of biomolecules, and the interactions between complexes. For example, large-scale motions occur and are often essential for biomolecule function, especially with regard to proteins. Theoretical approaches developed for folding which incorporate the interplay between energetics and configurational entropy can now be utilized to study protein function. Discovering the physical and molecular aspects of protein binding underpins the understanding of all cellular functions.

Protein folding has long been viewed as being rich in complexities. With the development of the energy landscape theory, our view of protein folding, however, has greatly simplified from the hopelessly complex one first presented by Levinthal’s paradox.

Essentially, most of the biological functions of DNA require the binding of specific proteins to specific DNA sequences. For binding to occur, the protein has to discriminate between many similar and competing binding sites. It must not only recognize the DNA site, but also find the appropriate target rapidly, and tightly bind to one having the special features and corresponding biological function that distinguishes it from the millions of competing and overlapping non-specific sites.