TABLE 1.
Calculated binding free energy
| Potential binding sitea | Avg free energy (ΔG) ± SDb
|
|
|---|---|---|
| CRK SH2 | CRKL SH2 | |
| FGFR1 autophosphorylation sites | ||
| pY463 (GVSEpYELPEDPRWELPR) | −231.44 ± 21.90 | −343.99 ± 32.63 |
| pY583/pY585 (PGLEpYCpYNPSHNPEEQLSS) | −113.38 ± 39.06 | −220.74 ± 27.41 |
| pY653/pY654* (HHIDpYpYKKTTNGRLPVKW) | ND | ND |
| pY730 (TNELpYMMMRDCWHAVPS) | −268.08 ± 29.44 | −379.22 ± 18.95 |
| pY766 (SNQEpYLDLSMPLDQYSP) | −167.49 ± 24.39 | −247.40 ± 17.28 |
| CRK/CRKL internal sites | ||
| p221 in CRK (EPGPpYAQPSVNTPLPNL) | −262.85 ± 39.02 | ND |
| p207 in CRKL (PAHApYAQPQTTTPLPAV) | ND | −268.40 ± 13.56 |
a
Amino acid sequences used for simulation are given in single-letter code in parentheses; pY (indicated in boldface) denotes a phosphotyrosine. *, Y653/Y654 locate within the activation loop of the catalytic domain and are therefore omitted in the current analysis.
b
The values are shown as averages from structures extracted every 10 ps between 4 and 5 ns of simulations in kcal/mol. ND, not determined.