HAPTIC: Heuristic Affinity Prediction Tool for Immune Complexes

Use HAPTIC to estimate affinity of paratopes for cognate flexibly disordered peptidic antigens, allowing for variable-length B-cell epitopes.

Paratope-footprint radius (Å):
Temperature of immunization (K):
Temperature of immunoassay (K):
Input peptidic sequence data (FASTA format):

Sample HAPTIC Input and Output:

No. Input Output Temperature (K)
Immunization Immunoassay
1 example1.faa example1.htm 310.15 277.15
2 example2.faa example2.htm 310.15 293.15
3 example3.faa example3.htm 310.15 298.15
4 example4.faa example4.htm 312.35 277.15
5 example5.faa example5.htm 312.35 293.15
6 example6.faa example6.htm 312.35 310.15

Notes:

  1. HAPTIC estimates epitope-paratope binding affinity as dissocation-constant values for variable-length candidate epitopes of conformationally disordered peptidic antigen sequences.
  2. Paratope-footprint radius (in Å) determines maximum length of rigid poly-L-proline II (PPII) helical segment (assuming 3.1 Å rise per residue) in a candidate epitope.
  3. Temperature of immunization is normal body temperature for immunized animal species (e.g., 310.15 K = 37°C for human/mouse [default] or 312.35 K = 39.2°C for rabbit).
  4. Temperature of immunoassay is for experiment to measure epitope-paratope binding affinity, with default value assumed for ambient/room temperature of 298.15K = 25°C.
  5. Input must be provided as peptidic sequence data in FASTA format using only the 20 standard amino-acid residue codes (ACDEFGHIKLMNPQRSTVWY).
  6. Posttranslational/other covalent modifications such as oxidation, phosphorylation and glycosylation are neglected.
  7. Each input sequence is partitioned into candidate epitopes (i.e., tripeptide and longer segments).
  8. Excessively long candidate epitopes (i.e., comprising excessively long run/s of consecutive proline residues and/or deemed too bulky to fit paratope) are excluded from analysis.
  9. Candidate epitopes are ranked by estimated affinity at temperature of immunization, such that top-ranking candidate epitope is identified as predicted most immunodominant epitope.

References:

  1. Caoili SE (2006) A structural-energetic basis for B-cell epitope prediction. Protein & Peptide Letters 13(7):743-751 (PMID: 17018020)
  2. Caoili SE (2010) Immunization with peptide-protein conjugates: impact on benchmarking B-cell epitope prediction for vaccine design. Protein & Peptide Letters 17(3):386-398 (PMID: 19594433)
  3. Caoili SE (2012) On the meaning of affinity limits in B-cell epitope prediction for antipeptide antibody-mediated immunity. Advances in Bioinformatics 2012:346765, doi: 10.1155/2012/346765 (PMID: 23209458)
  4. Caoili SE (2014) Benchmarking B-cell epitope prediction with quantitative dose-response data on antipeptide antibodies: towards novel pharmaceutical product development. BioMed Research International 2014:867905, doi: 10.1155/2014/867905 (PMID: 24949474)
  5. Caoili SE (2014) Hybrid methods for B-cell epitope prediction. Methods in Molecular Biology 1184:245-283, doi: 10.1007/978-1-4939-1115-8_14 (PMID: 25048129)
  6. Caoili SE (2015) An integrative structure-based framework for predicting biological effects mediated by antipeptide antibodies. Journal of Immunological Methods 427:19-29, doi: 10.1016/j.jim.2015.09.002 (PMID: 26410103)
  7. Caoili SE (2021) Beyond B-cell epitopes: curating positive data on antipeptide paratope binding to support peptide-based vaccine design. Protein & Peptide Letters 28(8):953-962, doi: 10.2174/0929866528666210218215624 (PMID: 33602065)
  8. Caoili SE (2022) Prediction of variable-length B-cell epitopes for antipeptide paratopes using the program HAPTIC. Protein & Peptide Letters (online ahead of print), doi: 10.2174/0929866529666220203101808 (PMID: 35125075)

Author Information:

Salvador Eugenio C. Caoili (email: badong@post.upm.edu.ph)
Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila
Room 101, Medical Annex Building (Salcedo Hall), 547 Pedro Gil Street, Ermita, Manila 1000, Philippines
Telephone/Fax: +63 526 0377 / +63 526 4197