B-P.13: Identifying Candidate Precursors of Cyclic Repetitive Antibody Targets with the Peptidic Antigen Sequence Complexity Analyzer (PASCA)
Author
Biomedical Innovations Research for Translational Health Science (BIRTHS) Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila
Keywords
cyclic peptides, linear B-cell epitopes, paratopes, repetitive sequences, circular permutation, binding-mode degeneracy, relative perplexity
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Peptide sequences are potentially useful antibody targets, notably among synthetic constructs that can replace more complex, labile and/or hazardous antigens (e.g., pathogen virulence factors) in the manufacture of biomedical products (e.g., vaccines, immunodiagnostics and prophylactic/therapeutic antibodies). However, product development may fail due to structural differences between linear peptides and the intended final antibody targets, particularly where the peptide amino- and/or carboxy-termini correspond to internal protein-sequence positions in those targets. Yet, such structural mismatching can conceivably be avoided by using repetitive peptide sequences (e.g., tandem repeats) in cyclic rather than linear form. Hence, the present work provides the Peptidic Antigen Sequence Complexity Analyzer (PASCA) for identifying candidate precursors of cyclic repetitive antibody targets in FASTA-formatted input data comprising linear B-cell epitopes (LBCEs). PASCA characterizes peptidic (e.g., peptide and protein) antigens with regard to repetitive-sequence content quantified as paratope-binding degeneracy z, itself estimated as a lower bound on the relative perplexity of paratope-binding modes among circularly permuted sequence segments representing LBCEs and defined by a sliding window, z thus being unity for homopolymers and the reciprocal of sequence length for nondegenerate sequences. PASCA forms part of the PASCA User Toolkit (PUT), which also comprises the PASCA-associated Utility for Matrix Assignment (PUMA) and the PASCA-associated Utility for Sequence Selection (PUSS). PUMA provides for user-defined alternatives to the default residue-similarity matrix of Boltzmann weights used by PASCA to evaluate z, whereas PUSS facilitates preparation of PASCA input sequence data (e.g., from the Immune Epitope Database [https://iedb.org/]). All of PUT is freely accessible online (https://freeshell.de/badong/put.htm).
Co-authors: None
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