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![[Figure 9]](nz5014fig9mag.jpg)
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Figure 9
Crystal and binding-site bottleneck radii and their relation to the minimum projection radii of the conformational ensembles of the soaked small molecules. (a) The crystal bottleneck radii are plotted against the minimum of the minimum projection radius of the conformational ensemble of the individual soaked molecules. (b) The bottleneck radii observed in front of the small-molecule-binding site are plotted against the minimum of the minimum projection radius of the conformational ensemble of the molecule. The line of identity is provided to highlight false-negative results. The points are colored according to the kernel-density estimate using Gaussian kernels visualizing highly occupied regions in the data set. (c) The modeled structures of flexible loops that lack proper electron-density support, leading to false-negative predictions with LifeSoaks as shown for the structure of the human protein kinase CDK2 (PDB entry 4ez7). The atom and cartoon representations are colored according to their EDIAm values. The electron density (2Fo − Fc) is shown in grid representation at a sigma level of 2. (d) Huge domain movements because of induced-fit phenomena resulting in false-negative LifeSoaks predictions, as illustrated by the structure of prolyl endopeptidase from Aeromonas caviae (PDB entry 3muo, blue). The original structure of the proteins in the crystals used for soaking highlights the accessibility of the binding site in the ligand-free crystal of the structure (PDB entry 3ium, cyan). The binding site is highlighted by the corresponding ligands in stick representation (ZPR_A_701 and ZPR_B_702, magenta). (c) and (d) were generated with PyMOL (Schrödinger). |
![[Figure 9]](nz5014fig9.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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