Methods and systems for predicting misfolded protein epitopes
AssigneeThe University of British Columbia
InventorsNeil R. Cashman, Steven S. Plotkin, William C. Guest
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Abstract
A method and system to identify an epitope unique to a misfolded form of a protein is provided. Sets of one or more amino acid residues are selected from a model representing the structure of the protein; the free energy of unfolding of each set is determined; and the epitope is identified from the sets having a total probability of unfolding above a minimum probability or a free energy of unfolding below a minimum energy. In other aspects, the invention provides for the use of epitopes identified by the epitope prediction methods, and related antibodies, to diagnose and treat disease and to screen samples for the presence of such epitopes.
Claims15
A method for obtaining an immunogen useful to produce an antibody that binds selectively to a misfolded form of a protein relative to the natively folded form of that protein, the method comprising:
- applying a method of operating a system to identify an epitope unique to a misfolded form of a protein of interest, the system comprising a processor and one or more memories coupled to the processor, the one or more memories containing instructions recorded thereon that, when executed by the processor, cause the processor to:
- (a) receive a model representing at least a portion of the structure of the protein of interest;
- (b) select one or more sets from the model, each set comprising one or more amino acid residues;
- (c) determine the free energy of unfolding of each set;
- and
- (d) identify the epitope by:
- (i) determining the total probability of unfolding of each set based on the free energy of unfolding of one or more of the sets in isolation, and identifying the epitope from the sets having a total probability of unfolding above a minimum probability;
- or
- (ii) identifying the epitope from the sets having a free energy of unfolding below a minimum energy;
- wherein the identifying comprises storing data describing the epitope in the one or more memories of the system, or presenting graphical or numerical depiction of the epitope on a display or printed medium;
- preparing a peptide comprising the epitope identified in step (d) by solid or solution phase synthesis;
- and
- isolating the peptide and producing the immunogen comprising the peptide that comprises the epitope unique to the misfolded form of the protein of interest.
Dependencies are inferred from the claim text.