9E5F
Discovery of an Orally Bioavailable 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 | 0.1 M Sodium acetate, pH 4.6,30% PEG 4000 and 0.2M ammonium acetate | |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.45 | 49.85 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 40.175 | α = 90 |
| b = 53.63 | β = 90 |
| c = 90.206 | 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 PILATUS 6M | 2020-02-18 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | SSRL BEAMLINE BL9-2 | 0.979 | SSRL | BL9-2 |
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 | 1.35 | 53.63 | 99.5 | 0.04 | 0.04 | 0.01 | 1 | 26.4 | 12.6 | 43420 | 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 | 1.35 | 1.37 | 95.4 | 0.3 | 0.32 | 0.1 | 0.96 | 3.7 | 9 | ||||||||||
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 | 1.35 | 46.099 | 43359 | 2120 | 99.404 | 0.155 | 0.1535 | 0.1782 | 18.98 | ||||||||
| 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] | |
| -0.038 | -0.598 | 0.636 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 31.85 |
| r_dihedral_angle_6_deg | 16.356 |
| r_lrange_it | 12.6 |
| r_lrange_other | 11.988 |
| r_dihedral_angle_3_deg | 11.536 |
| r_dihedral_angle_other_2_deg | 7.628 |
| r_scangle_it | 6.462 |
| r_scangle_other | 6.46 |
| r_dihedral_angle_1_deg | 5.968 |
| r_mcangle_it | 4.722 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 1371 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 156 |
| Heterogen Atoms | 40 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| xia2 | data reduction |
| Aimless | data scaling |
| PHASER | phasing |
