System and method for determining three-dimensional structure of protein sequences

摘要

The present invention pertains to a system and method for predicting the protein fold of a target amino acid residue sequence of unknown protein structure. A target sequence is represented by a sequence of residue variability types that utilizes positional variability information present in an associated family of homologous sequences to the target sequence. The use of the positional variability information increases the likelihood of matching the target sequence with a known protein structure. In a first preferred embodiment, a target sequence is mapped into a sequence of residue variability types that are based on the solubility variability present between amino acid residues in homologous sequences. In a second preferred embodiment, each residue variability type represents a cluster of residue types at each position of aligned sets of homologous protein sequences. Each distinct cluster represents a pattern of residue variability at various positions in sets of homologous protein sequences. The sequence of residue variability types is aligned with one or more environment strings, each of which represents a known protein structure in accordance with the degree of surface exposure for each amino acid position in the protein's structure. The alignment is performed using a threading procedure that determines a score for each alignment indicating the compatibility of the sequence to the structure. The protein structure associated with the highest score is deemed to be the most analogous structure to the target sequence.