SUITE = PACT + INCA + SPIRE + RACE + LACE + SUIT

SUIT: SAPPHIRE User Interface Tool

Provide input for SAPPHIRE to estimate affinity of candidate B-cell epitopes:

Antibody footprint radius (Å):
Ionic/H-bond energy difference (kcal/mol):
Paratope sidechain DeltaSconf (cal/mol K Å^2):
Temperature of immunoassay (K):
Dissociation-constant cutoff value (M):
Excluded amino-acid residue/s:
A (ALA) C (CYS) D (ASP) E (GLU) F (PHE)
G (GLY) H (HIS) I (ILE) K (LYS) L (LEU)
M (MET) N (ASN) P (PRO) Q (GLN) R (ARG)
S (SER) T (THR) V (VAL) W (TRP) Y (TYR)
Peptidic-structure ASA data (naccess-style format [e.g., generated using naccess via INCA]):

Optional query peptide sequence/s (1-letter code, raw format [with one sequence per line]):

Sample SUIT Input (from INCA) and Output:

No. Input Output Query Temperature (K)
1 epospdbv.asa epospdbv.out epoquery.raw 277.15
2 renspdbv.asa renspdbv.out renquery.raw 277.15
3 ifnpacto.asa ifnpacto.out ifnquery.raw 298.15
4 urepdbxr.asa urepdbxr.out urequery.raw 277.15
5 toxpacto.asa toxpacto.out toxquery.raw 298.15
6 ps1pacto.asa ps1pacto.out ps1query.raw 277.15
7 ps2pacto.asa ps2pacto.out ps2query.raw 293.15
8 ps3pacto.asa ps3pacto.out ps3query.raw 298.15

Notes:

  1. SUIT reports estimated dissocation-constant values for candidate epitopes of peptidic antigen structure.
  2. Antibody-footprint radius (in Å) determines candidate-epitope length (in residues, assuming 3.5 Å contour length per residue).
  3. Ionic/H-bond energy difference accounts for greater binding-affinity contribution of charged relative to uncharged polar functional groups.
  4. Paratope sidechain DeltaSconf (per unit ASA of candidate epitope) accounts for contribution of paratope sidechains to conformational-entropy change upon binding with epitope.
  5. Temperature of immunoassay is selected for initial binding step (e.g., of antibody-antigen preincubation), with default value assumed for ambient/room temperature of 298.15 K (i.e., 25°C).
  6. Dissociation-constant cutoff value determines predicted immunizing-peptide sequences in SUIT output, such that estimated dissociation constant for each candidate epitope in those sequences is below cutoff value.
  7. Excluded amino-acid residue/s can be specified to restrict the allowed set of predicted immunizing-peptide sequences (e.g., such that they are devoid of the readily oxidized residues Cys, Met and Trp).
  8. Optionally, query peptide sequences (e.g., from literature or other programs) can be evaluated for perfect (i.e., 100% identity) matches to peptidic antigen. For each match thus found, the candidate epitope having the lowest estimated dissociation-constant value is reported (e.g., so the said value may be compared with a corresponding experimentally obtained value).
  9. Posttranslational modifications such as glycosylation and phosphorylation are not considered at this time. Posttranslational proteolytic processing may, however, be simulated by deleting the appropriate residues from the antigen structure prior to computation of ASA.