Systems and methods for predicting active site residues in a protein
AssigneeStructural Genomix, Inc.
InventorKetan S. Gajiwala
Life of this patent
Estimating the term…
Abstract
A system and method for predicting the active site residues in a target protein. The target protein, referred to interchangeably as the-target amino sequence or the target sequence, is pairwise aligned with a set of query sequences. Using these multiple pairwise sequence alignments, residue positions within the target sequence which satisfy specified sequence-based criteria are identified as candidate active site positions. Candidate active site positions are mapped to a three-dimensional representation of the target sequence and filtered against structure-based criteria. Positions within the target sequence that satisfy both the sequence-based and structure-based criteria are predicted to be active site residues.
Claims60
A method for selecting a plurality of candidate active site positions in a target sequence, the method comprising:
- aligning each query sequence in a plurality of query sequences to said target sequence to form a set of aligned query sequences;
- choosing a subset of aligned query sequences from said set of aligned query sequences, each aligned query sequence in said subset of aligned query sequences satisfying a predetermined criterion;
- identifying substitution types for each residue position i in said target sequence, each substitution type characterized by a difference between (i) a residue identity at a residue position i in an aligned query sequence in said subset of aligned query sequences and (ii) said residue identity at said residue position i in said target sequence;
- and
- selecting said plurality of candidate active site positions, each candidate active site position in said plurality of candidate active site positions identified as a residue position i in said target sequence in which (i) a residue identity at said residue position i in said target sequence is in an allowed class of amino acids, (ii) each substitution type identified for said residue position i in said identifying step is in an allowed class of substitution types, and (iii) a threshold percentage of said subset of aligned query sequences include a residue that is aligned with said residue position i in said target sequence.
A computer program product for use in conjunction with a computer having a processor, said computer program product comprising a computer readable storage medium and a computer program mechanism embedded therein, the computer program mechanism for selecting a plurality of candidate active site positions in a target sequence, the computer program mechanism causing the processor to execute the steps of:
- aligning a plurality of query sequences to said target sequence to form a set of aligned query sequences;
- choosing a subset of aligned query sequences from said set of aligned query sequences, each aligned query sequence in said subset of aligned query sequences satisfying a predetermined criterion;
- identifying substitution types for each residue position i in said target sequence, each substitution type characterized by a difference between (i) a residue identity at a residue position i in an aligned query sequence in said set of aligned query sequences and (ii) said residue identity at said residue position i in said target sequence;
- and
- selecting a plurality of candidate active site positions, each candidate active site position in said plurality of candidate active site positions identified as a residue position i in said target sequence in which (i) a residue identity at said residue position i in said target sequence is in an allowed class of amino acids, (ii) each substitution type identified for said residue position i in said target sequence is in an allowed class of substitution types, and (iii) a threshold percentage of said set of aligned query sequences includes a residue that is aligned with said residue position i in said target sequence.
A computer readable memory used to direct a client/server system to function in a specified manner, comprising:
- an alignment module for aligning a plurality of query sequences;
- said alignment module including executable instructions stored in said computer readable memory, said executable instructions including:
- instructions for reading a plurality of query sequences from an amino acid sequence database;
- instructions for aligning said plurality of query sequences to a target sequence in order to form a set of aligned query sequences;
- and
- instructions for choosing a subset of aligned query sequences from said set of aligned query sequences, each aligned query sequence in said subset of aligned query sequences satisfying a predetermined criterion;
- and
- a control module for using said aligned set of query sequences to select a plurality of candidate active site positions in said target sequence, said control module including executable instructions stored in said computer readable memory, said executable instructions including:
- instructions for identifying substitution types for each residue position i in said target sequence, each substitution type characterized by a difference between (i) a residue identity at a residue position i in an aligned query sequence in said set of aligned query sequences and (ii) said residue identity at said residue position i in said target sequence;
- and
- instructions for selecting said plurality of candidate active site positions based on a sequence-based criterion that each candidate active site position in said plurality of candidate active site positions is a residue position i in said target sequence in which (i) a residue identity at said residue position i in said target sequence is in an allowed class of amino acids, (ii) each substitution type identified for said residue position i in said target sequence is in an allowed class of substitution types, and (iii) a threshold percentage of said set of aligned query sequences includes a residue that is aligned with said residue position i in said target sequence.
Dependencies are inferred from the claim text.