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Arg could extend to the bottom of pocket F of A*6801 and A*3101, forming
complex stabilizing hydrogen bonds with residues at the bottom of the pocket.
Among the secondary anchors, positions 1, 3, 5, 6, and 7 were of great importance.
The common favored property for position 1 was hydrogen-bond donor/acceptor
ability. Hydrogen-bond donor groups with negative electrostatic potential were pre-
ferred at position 3 for three of the alleles. Sidney and co-workers (Sidney et al.
1996)
found that peptides with an aromatic residue, like Tyr, Phe, and Trp, had a 31-
fold increase in binding affinity to A*0301. Bulky side chains with negative electro-
static potential were preferred at position 5. Hydrogen-bond donors and acceptors
were disfavored here. Hydrophilic amino acids capable of forming hydrogen bonds
were well accommodated at position 6. The only common favored property for posi-
tion 7 was hydrophobicity. Positions 4 and 8 face the T-cell receptor (Silver, Guo,
Strominger, and Wiley 1992),
but can still contribute to the affinity. Hydrogen-bond
donor ability was important for position 4. Steric bulk and negative electrostatic
potential were favored at position 8.
Looking at the CoMSIA results for the mouse alleles, we see that with the H2-D
b
allele, steric bulk is favored with the side chains of positions 3 and 6 falling into
pockets D and C, respectively. For the electrostatic potential field, the alkyl side
chain of position 1 falls into pocket A which consists of Val and Ser residues (Saper
et al. 1991). At position 2, where the side chain falls into pocket B, electrostatic
potential interaction is favored (Saper et al. 1991). In the remaining positions there
are no favorable electrostatic potential interactions. There is a strongly favored hy-
drophobic interaction at position 8 where the side chain is solvent exposed and con-
tacts the T-cell. The major favored interactions of the hydrogen bond donor fields are
found at position 1 and across the peptide backbone between positions 3 and 4. The
hydrogen bond acceptor map shows position 2 to be favored and, to a lesser extent,
at positions 5 and 7.
For the H2-K
b
allele, steric bulk is favored at positions 1, 3, 4, and 5. The side
chain at position 1 makes a weak electrostatic interaction; while at position 2 the
electrostatic potential map indicates that aromatic-type residues, such as Tyr or Phe,
are well tolerated. This is in good agreement with experimental data (Ruppert et al.
1993; Parker, Bednarek, and Coligan 1994).
There is no major interaction between
side chains at position 3 and pocket D indicated by our model, and in the remaining
positions there are no clear favorable electrostatic interactions. The hydrophobic
interaction field identifies a favorable interaction at positions 3 and 5. Pocket D is a
hydrophobic cavity and amino acids such as Tyr and Ile are well tolerated here
which would significantly deepen the depth and volume of pocket D (Fremont et al.
1992). The major favored interactions of the hydrogen bond donor fields are found at
positions 1, 3, and 4 (pockets A, D and the “flag” pocket, respectively) (Saper et al.
1991), with a major disfavored interaction found at position 6 (pocket C). The
hydrogen bond acceptor map has favoured interactions at positions 1 and 4, pocket A
and the “flag” pocket, respectively, but major disfavored interactions between the
side chain positions 3 and 5.
For the H2-K
k
allele, steric bulk field is favored at positions 1, 7, and 8. There is
no favorable electrostatic interaction at position 1, while at position 2 electrostatic
potential is favored. Position 3 falls into pocket D but makes little interaction with
