Global characteristics of protein sequences and their implications.

Computational studies of the relationships between protein sequence, structure, and folding have traditionally relied on purely local sequence representations. Here we show that global representations, on the basis of parameters that encode information about complete sequences, contain otherwise inaccessible information about the organization of sequences. By studying the spectral properties of these parameters, we demonstrate that amino acid physical properties fall into two distinct classes. One class is comprised of properties that favor sequentially localized interaction clusters. The other class is comprised of properties that favor globally distributed interactions. This observation provides a bridge between two classic models of protein folding-the collapse model and the nucleation model-and provides a basis for understanding how any degree of intermediacy between these two extremes can occur.