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Garriott: The docking cone is designed to where you can be off target by even up to half a meter, really, and it will funnel you into the correct docking.
Because this software energy (scoring) function, similarly to others used in computational docking, is usually not enough to discriminate the correct docking pose from other poses48, the 100 top-ranking possible ligand positions were generated by the Vina software, and the best one was chosen according to the biochemical rationales.
Our analyses focus on both the ability of the programs to generate a correct docking pose and to top-rank it.
The correct docking program enables to find true inhibitors among a large number of inactive compounds.
The final structure was chosen on the basis of the docking score and presumed to represent the spatially correct docking.
In the absence of a co-expressed Cx26WT protein, or possibly another connexin (e.g. Cx30), the conformational change will eventually prevent correct docking of opposing hemichannels.
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This may explain why the top-rank pose was correct after docking but not after rescoring.
Hence, they can discriminate more reliably between correct and incorrect docking poses.
We also chose to deliberately overpredict the interface, relying on the HADDOCK scoring function to discriminate between correct and incorrect docking solutions.
Their approach to include flexibility yielded better energetic discrimination between correct and incorrect docking models and a significant improvement in the quality of their predictions.
Here, we show that Drosophila Syp is present in the muscle and required for correct vesicle biogenesis, docking, and neurotransmitter release from the pre-synapse.
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