A method for computer-based prediction of one or more candidate epitopes in a protein, the method comprising: providing, on a computer system, a conformational sampling engine; obtaining, at the computer system, a model of a protein suitable for use with the conformational sampling engine, the obtained protein model comprising a native structure; applying, by the computer system, a collective coordinate bias to the protein model, the collective coordinate bias causing the conformational sampling engine to in turn force the protein model to at least partially unfold from its native structure to an updated structure, wherein the collective coordinate bias is applied globally to at least a substantial portion of the protein model and is impartial as to where, within the substantial portion of the protein model, unfolding occurs, and wherein applying the collective coordinate bias to the protein model comprises increasing, decreasing or otherwise varying or manipulating an externally applied target collective coordinate to apply a corresponding biasing potential to the protein model and performing, by the computer system, a discrete time simulation on the protein model over a plurality of time steps, the discrete time simulation starting with the native structure for the protein model and, in each particular time step from among the plurality of time steps, generating a corresponding updated structure for the protein model for the particular time step; and analyzing, by the computer system, the updated structure to identify one or more candidate epitopes, wherein a candidate epitope is a group of residues that exhibits one or more indicia of localized unfolding.. providing, on a computer system, a conformational sampling engine; obtaining, at the computer system, a model of a protein suitable for use with the conformational sampling engine, the obtained protein model comprising a native structure; applying, by the computer system, a collective coordinate bias to the protein model, the collective coordinate bias causing the conformational sampling engine to in turn force the protein model to at least partially unfold from its native structure to an updated structure, wherein the collective coordinate bias is applied globally to at least a substantial portion of the protein model and is impartial as to where, within the substantial portion of the protein model, unfolding occurs, and wherein applying the collective coordinate bias to the protein model comprises increasing, decreasing or otherwise varying or manipulating an externally applied target collective coordinate to apply a corresponding biasing potential to the protein model and performing, by the computer system, a discrete time simulation on the protein model over a plurality of time steps, the discrete time simulation starting with the native structure for the protein model and, in each particular time step from among the plurality of time steps, generating a corresponding updated structure for the protein model for the particular time step; and analyzing, by the computer system, the updated structure to identify one or more candidate epitopes, wherein a candidate epitope is a group of residues that exhibits one or more indicia of localized unfolding..