Summary: How and why phosphotyrosine-containing peptides bind to the
SH2 and PTB domains
Yingyao Zhou and Ruben Abagyan
Background: Specific recognition of phosphotyrosine-containing protein
segments by Src homology 2 (SH2) and phosphotyrosine-binding (PTB)
domains plays an important role in intracellular signal transduction. Although
many SH2/PTB-domain-containing receptor­peptide complex structures have
been solved, little has been done to study the problem computationally.
Prediction of the binding geometry and the binding constant of any
peptide­protein pair is an extremely important problem.
Results: A procedure to predict binding energies of phosphotyrosine-
containing peptides with SH2/PTB domains was developed. The average
deviation between experimentally measured binding energies and theoretical
evaluations was 1.8 kcal/mol. Binding states of unphosphorylated peptides
were also predicted reasonably well. Ab initio predictions of binding geometry
of fully flexible peptides correctly identified conformations of two pentapeptides
and a hexapeptide complexed with a v-Src SH2 domain receptor with root
mean square deviations (rmsds) of 0.3 Å, 1.2 Å and 1.5 Å, respectively.
Conclusions: The binding energies of phosphotyrosine-containing complexes
can be effectively predicted using the procedure developed here. It was also

Source: Abagyan, Ruben - School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego

Collections: Biology and Medicine