9E5D
Discovery of an Orally Biovailable KRAS G12D Inhibitor
X-RAY DIFFRACTION
Starting Model(s)
| Initial Refinement Model(s) | |||
|---|---|---|---|
| Type | Source | Accession Code | Details |
| experimental model | PDB | 6ZLI | |
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, SITTING DROP | 293 | 0.2M (NH4)3 Citrate, 20% (w/v) PEG 3350 | |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.41 | 48.99 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 40.04 | α = 90 |
| b = 53.71 | β = 90 |
| c = 88.85 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | P 21 21 21 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 100 | PIXEL | DECTRIS EIGER2 X 9M | 2021-02-09 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | APS BEAMLINE 17-ID | 1 | APS | 17-ID |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | CC (Half) | Net I Over Average Sigma (I) | Redundancy | Number Reflections (All) | Number Reflections (Observed) | Observed Criterion Sigma (F) | Observed Criterion Sigma (I) | B (Isotropic) From Wilson Plot | |||||
| 1 | 1.36 | 45.96 | 87 | 0.063 | 0.069 | 0.027 | 0.998 | 14.1 | 5.7 | 33993 | 12.9 | ||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | CC (Half) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||
| 1 | 1.36 | 1.43 | 37.8 | 0.69 | 0.86 | 0.51 | 0.54 | 1.1 | 2.3 | ||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | Resolution (High) | Resolution (Low) | Number Reflections (Observed) | Number Reflections (R-Free) | Percent Reflections (Observed) | R-Factor (All) | R-Work | R-Free | Mean Isotropic B | ||||||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | FREE R-VALUE | 1.36 | 45.96 | 33976 | 1690 | 80.909 | 0.168 | 0.1667 | 0.193 | 17.896 | ||||||||
| Temperature Factor Modeling | ||||||
|---|---|---|---|---|---|---|
| Anisotropic B[1][1] | Anisotropic B[1][2] | Anisotropic B[1][3] | Anisotropic B[2][2] | Anisotropic B[2][3] | Anisotropic B[3][3] | |
| 1.056 | 0.03 | -1.086 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 28.613 |
| r_dihedral_angle_6_deg | 17.133 |
| r_dihedral_angle_3_deg | 11.575 |
| r_lrange_it | 10.28 |
| r_lrange_other | 10.277 |
| r_dihedral_angle_other_2_deg | 7.728 |
| r_dihedral_angle_1_deg | 6.439 |
| r_scangle_it | 6.311 |
| r_scangle_other | 6.309 |
| r_scbond_it | 4.357 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 1350 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 123 |
| Heterogen Atoms | 49 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| autoPROC | data reduction |
| autoPROC | data scaling |
| PHASER | phasing |
