Analyzing the sequence-structure relationship of a library of local structural prototypes.

We present a thorough analysis of the relation between amino acid sequence and local three-dimensional structure in proteins. A library of overlapping local structural prototypes was built using an unsupervised clustering approach called "hybrid protein model" (HPM). The HPM carries out a multiple structural alignment of local folds from a non-redundant protein structure databank encoded into a structural alphabet composed of 16 protein blocks (PBs). Following previous research focusing on the HPM protocol, we have considered gaps in the local structure prototype. This methodology allows to have variable length fragments. Hence, 120 local structure prototypes were obtained. Twenty-five percent of the protein fragments learnt by HPM had gaps. An investigation of tight turns suggested that they are mainly derived from three PB series with precise locations in the HPM. The amino acid information content of the whole conformational classes was tackled by multivariate methods, e.g., canonical correlation analysis. It points out the presence of seven amino acid equivalence classes showing high propensities for preferential local structures. In the same way, definition of "contrast factors" based on sequence-structure properties underline the specificity of certain structural prototypes, e.g., the dependence of Gly or Asn-rich turns to a limited number of PBs, or, the opposition between Pro-rich coils to those enriched in Ser, Thr, Asn and Glu. These results are so useful to analyze the sequence-structure relationships, but could also be used to improve fragment-based method for protein structure prediction from sequence.