I-sites are short
sequence-structure motifs that are mined from the
Protein Data Bank
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained a ...
(PDB) that correlate strongly with three-dimensional structural elements. These sequence-structure motifs are used for the local structure prediction of proteins. Local structure can be expressed as fragments or as backbone angles. Locations in the protein sequence that have high confidence I-sites predictions may be the initiation sites of
folding. I-sites have also been identified as discrete models for folding pathways. I-sites consist of about 250 motifs. Each
motif has an amino acid profile, a fragment structure (represented by a "paradigm" fragment chosen from a protein in the PDB) and optionally, a 4-dimensional tensor of pairwise sequence covariance.
Construction of I-site Library
The sequence and structure database
The database initially consisted of 471 protein sequence families from the HSSP database, with an average of 47 aligned sequences per family. Each family contained a single known structure (parent) from the Brookhaven protein Data Bank. These were a subset of the PDBSelect-25 list, having no more than 25% sequence identity between any two alignments. Disordered loops were omitted. Gaps and insertions in the sequence were ignored.
Clustering of sequence segments
Each position in the database is described by a weighted amino acid frequency. A
similarity measure
In statistics and related fields, a similarity measure or similarity function or similarity metric is a real-valued function that quantifies the similarity between two objects. Although no single definition of a similarity exists, usually such mea ...
in sequence space between a segment (p) and a cluster of segments (q) is defined as: