Protein Foldability and Designability: General Physics and Pretty Chemistry

Abstract

Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to the lowest structrally dissimilar conformation), aside from leading to fast folding, are highly designable (in the sense that many sequences target onto it in the folding process). These results are quite general, do not depend on the particular simmetries displayed by the compact conformation chosen as native, and can be obtained making use of a large class of contact energies. On the other hand, the design of sequences which fold onto native conformations displaying secondary structures and eventually tertiary simmetries, is a difficult task requiring a delicate tuning of the contact energies.