title: Protein stability, flexibility and function.
abstract: Proteins rely on flexibility to respond to environmental changes, ligand binding and chemical modifications. Potentially, a perturbation that changes the flexibility of a protein may interfere with its function. Millions of mutations have been performed on thousands of proteins in quests for a delineation of the molecular details of their function. Several of these mutations interfered with the binding of a specific ligand with a concomitant effect on the stability of the protein scaffold. It has been ambiguous and not straightforward to recognize if any relationships exist between the stability of a protein and the affinity for its ligand. In this review, we present examples of proteins where changes in stability results in changes in affinity and of proteins where stability and affinity are uncorrelated. We discuss the possibility for a relationship between stability and binding. From the data presented is it clear that there are specific sites (flexibility hotspots) in proteins that are important for both binding and stability. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches.
authors.affiliation: Structural Biology and NMR Laboratory (SBiN-Lab), Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Teilum
authors.forename: Johan G
authors.initials: JG
authors.lastname: Olsen
authors.forename: Birthe B
authors.initials: BB
authors.lastname: Kragelund
mesh_terms: D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
chemical_list: D008024:Ligands; D011506:Proteins