Mt. Pisabarro et al., MOLECULAR MODELING OF THE INTERACTION OF POLYPROLINE-BASED PEPTIDES WITH THE ABL-SH3 DOMAIN - RATIONAL MODIFICATION OF THE INTERACTION, Protein engineering, 7(12), 1994, pp. 1455-1462
A molecular model of the interaction of polyproline-rich peptides with
the Abl-SH3 domain is proposed, based on docking calculations with th
e DOCK program coupled with molecular dynamics simulations. Two distin
ct binding modes of the peptide to the same aromatic-rich region (Tyr1
0, Phe12, Trp39, Trp50, Tyr55) of the domain were obtained. It is prop
osed that these two models could represent different binding modes of
proline-rich peptides to Src homology region 3 domains. Several peptid
e mutants were designed to determine whether the two orientations were
possible. Analysis of the K-d values and fluorescence emission of the
se peptides indicate that one of the orientations is more plausible an
d that residues at position 4 of the peptide interact with the RT loop
, being important in modulating the peptide affinity for the Abl-SH3 d
omain.