Patent ID: 8452542

Claim:
A computer-implemented method of scoring a set of residues within a cluster of proteins from an initial set of three dimensional protein structures, comprising: identifying, by a computer, the initial set of three dimensional protein structures, each comprising a polypeptide sequence and structural coordinates; generating, by the computer, a plurality of pair-wise protein structure alignments of the set of three dimensional protein structures; for each pair of protein structures in the set: generating, by the computer, a first plurality of fragments from a first protein structure in the pair and a second plurality of fragments from a second protein structure in the pair, wherein each fragment is a polypeptide sequence of contiguous residues of a pre-determined length and has associated distances of structural coordinates of contiguous residue pairs; identifying, by the computer, a plurality of contiguous residue pairs from the first plurality of fragments and the second plurality of fragments having structural coordinates within the first pre-determined distance and having a pre-determined length, thereby identifying a plurality of pair-wise candidate spans for the pair; determining, by the computer, a pair-wise local similarity value that indicates the number of first plurality of fragments and second plurality of fragments that share candidate spans; determining, by the computer, a pair-wise global similarity value that indicates a number of residues that form a plurality of residue pairs from the first protein structure and the second protein structure, wherein a structural coordinate of each member of the residue pair falls within a second pre-determined distance based on the pair-wise structural alignment; generating, by the computer, a cluster of protein structures from the initial set of protein structures using the identified pair-wise candidate spans, the pair-wise local similarity values, and the pair-wise global similarity values; aligning, by the computer, all protein structures in the cluster to generate a one-to-one residue correspondence of the residue pairs for the cluster of protein structures; identifying, by the computer, a span from the cluster of protein structures, wherein each span comprises a set of one-to-one correspondences of residues that are within the first pre-determined distance of each other and within the second pre-determined distance based on the plurality of pair-wise structural alignments of the cluster of protein structures; generating, by the computer, a plurality of conservation scores for the cluster of protein structures, wherein the conservation scores are calculated for a plurality of residues within the span based on a metric for residue similarity; and storing, by the computer, the plurality of conservation scores, thereby scoring the set of residues within the cluster of protein structures.