Protein Interaction, Association and Fibrillation

A protein can fold efficiently with high fidelity if on average native contacts survive longer than non-native ones. If native contacts survive long enough to obtain a certain level of probability that other native contacts form before the first interacting unit dissociates this provides the folding process with directionality towards the native state and no particular pathway is needed. Interactions among hydrophobic residues are by far more important than electrostatic interactions in protein assembly, folding and stability. Proteins may under certain conditions and as a function of time give up their native folded state and form amyloid fibrils – a process that is involved in a number of human diseases. The fibrillation process can be perturbed by the presence of foreign surfaces, for example nanoparticles of different surface character. Introduction Protein folding and protein folds reflect the large number of non-covalent interactions that form under the very substantial constraints imposed by the covalent chain. Due to steric overlap, roughly ninety percent of the combinations of backbone torsion angles phi and psi are inaccessible. Nevertheless, the accessible ~10% of the Ramachandran map allows for a remarkable variation in protein folds through combinations of extended or helical segments 183 http://www.beilstein-institut.de/Bozen2008/Proceedings/Linse/Linse.pdf Systems Chemistry, May 26 – 30, 2008, Bozen, Italy