The generation and evaluation of molecular complexes in order to predict binding modes of protein ligand complexes, is still a challenging task.
As reported in the review article by Luscombe et al. [ 30], protein-DNA interactions can be grouped into eight different structural/functional groups based on the structures of the DNA-binding region in the proteins, which is also referred to as the binding mode of the protein [ 30- 32].
In this study, a reliable 3D structure for transmembrane (TM) region of mouse TRESK (mTRESK) was constructed, and then the reasonable blocker binding mode of the protein was investigated.
When the binding mode of the protein is unclear, we recommend trying the parameter sets for sharp and broad peaks.
This is unlike the ATP binding mode of typical protein kinases (18), which use the conserved, ATP-binding motif GxGxxGxV (x, any amino acid), not found in PI3KCs and PI3K-related kinases.
Liebschner, D. et al. Elucidation of the phosphate binding mode of DING proteins revealed by subangstrom X-ray crystallography.
Although most of the drugs commercially available have emerged through conventional drug discovery methods such as high-throughput screening (HTS), computational methods and functional assays, it is the structural information provided by the three-dimensional (3D) atomic structures that discloses details regarding the binding mode of such proteins.
A thorough understanding of the binding mode of this small protein, and its other family members, could be very informative in the design of potent neutralizing molecules of pro-inflammatory mediators of the immune system, such as chemokines.
As previously described (Park 2009), an appropriate parameter set for peak calling depends on the binding mode of the target protein.
