AUTOMATED PROTEIN-SEQUENCE DATABASE CLASSIFICATION - II - DELINEATIONOF DOMAIN BOUNDARIES FROM SEQUENCE SIMILARITIES

Motivation: Decomposing each protein into modular domains is a basic p rerequisite to classify accurately structural units in biological mole cules. Boundaries between domains are indicated by two similar- amino acid sequence segments located within the same protein (repeats) ol wi thin homologous proteins at notably different distances from their res pective N- or C-termini. Results: We have developed an automated metho d that combines such positional constraints derived from various detec ted pairwise sequence similarities to delineate the modular organizati on of proteins. The procedure has been applied to a non-redundant data set of 26 990 proteins whose sequences were taken from the PIR and SW ISS-PROT databanks and shared <60% sequence identity amongst pairs. Th e resultant clustering, delineation and multiple alignment of 24 380 s equence fragments yielded a new database of 4364 domain families. Comp arison of the domain collection with that of PRODOM indicates a clear improvement in the number and size of domain families, domain boundari es and multiple sequence alignments. The accuracy and sensitivity of t he method are illustrated by results obtained for ankyrin-like repeats and EGF-like modules.