Figure 4. Frequency of P-site/catalytic site interactions in iterative simulations of the EGFR self-phosphorylation event.

The frequencies of stable interactions of individual P-sites with the catalytic site were tabulated following 420 total molecular simulations, each performed using an initial structure randomly selected from a set of five hundred dimeric EGFR structures with randomized CT domain conformations (see Fig. 3). Interactions of individual P-sites in the CT domains of the receiver and activator molecules are separately tabulated, as are the sums of interactions of the P-sites in both chains (cis and trans). Note there was a general trend of reduced frequency of P-site/catalytic site binding events with increasing residue number, with the kinase-proximal site P-site-992 showing the most frequent interactions. Also, the catalytic site interactions of P-site-992 occurred exclusively in cis versus in trans.