Structure-based Design of Novel Chk1 Inhibitors: Insights into Hydrogen Bonding and Protein-Ligand Affinity
X-RAY DIFFRACTION
Starting Model(s)
| Initial Refinement Model(s) | |||
|---|---|---|---|
| Type | Source | Accession Code | Details |
| experimental model | PDB | 1IA8 | PDB ENTRY 1IA8 |
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | 7.5 | pH 7.50 | ||
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.9 | 56.9 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 45.116 | α = 90 |
| b = 65.909 | β = 101.38 |
| c = 54.582 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | P 1 21 1 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 100 | CCD | M | SINGLE WAVELENGTH | ||||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | APS BEAMLINE 19-ID | APS | 19-ID | |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge I (Observed) | 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 | 2.12 | 30 | 96.1 | 0.05 | 10.2 | 5.1 | 17903 | 2 | |||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||||
| 1 | 2.12 | 2.2 | 89.7 | 0.31 | 3.4 | 4.5 | |||||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | Starting model | Resolution (High) | Resolution (Low) | Number Reflections (Observed) | Number Reflections (R-Free) | Percent Reflections (Observed) | R-Factor (Observed) | R-Work (Depositor) | R-Work (DCC) | R-Free (Depositor) | R-Free (DCC) | R-Free Selection Details | Mean Isotropic B | ||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | PDB ENTRY 1IA8 | 2.2 | 30 | 14865 | 788 | 97.6 | 0.228 | 0.226 | 0.23 | 0.281 | 0.28 | RANDOM | 35.48 | ||||
| Temperature Factor Modeling | ||||||
|---|---|---|---|---|---|---|
| Anisotropic B[1][1] | Anisotropic B[1][3] | Anisotropic B[2][2] | Anisotropic B[3][3] | |||
| -2.03 | -1 | -0.13 | 1.77 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_1_deg | 4.381 |
| r_angle_other_deg | 1.089 |
| r_scangle_it | 1.086 |
| r_angle_refined_deg | 0.996 |
| r_mcangle_it | 0.833 |
| r_scbond_it | 0.602 |
| r_mcbond_it | 0.453 |
| r_nbd_other | 0.18 |
| r_symmetry_vdw_other | 0.163 |
| r_nbd_refined | 0.158 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2127 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 229 |
| Heterogen Atoms | 25 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| DENZO | data reduction |
| SCALEPACK | data scaling |
| AMoRE | phasing |
