STRUCTURE-BASED VIRTUAL SCREENING

Structure-based virtual screening utilizes the 3D structure of the target when searching for new hits. During the screening, predicted 3D structures of small molecules are fitted into the binding site of the experimentally determined or modeled 3D structure of the target (docking calculation). The 3D structures of thousands of large macromolecules have been already determined by X-ray crystallography or NMR spectroscopy and can be easily selected or uploaded in Mcule. Small molecules predicted to form critical interactions with the target get better (more negative) docking scores and are ranked higher.

  1. Go to HIT IDENTIFICATION / STRUCTURE-BASED VIRTUAL SCREEN
  2. Select the input collection if other than all Purchasable compounds of the Mcule database
  3. The loaded template workflow includes a number of individual workflow steps that will be executed sequentially on the input collection. You can adjust the parameters of the individual workflow steps. Detailed description of the available workflow steps and their parameters can be found HERE.
  4. Try to set different property ranges in the “Basic property filter” step. Click on “+ ADD CONDITION” to add another “Condition”, and click on the “X” button next to a “Condition” to remove it.
  5. Set the target for the "Docking (Vina)" workflow step. You can upload a PDB file (3D structural data for your target) or search by keyword and select from ~10,000 prepared target structures.
  6. You can also add new workflow steps by clicking on the “ADD WORKFLOW STEP” button on the right at the end of the workflow. Detailed description of the available workflow steps can be found HERE.
  7. After finalizing your workflow, you can set the “Name” and “Description” of the output collection and the “Maximum hits”. If you don't want to limit the number of hits in the output, you can delete the number from this field. Note that the maximum number of molecules in a single collection is limited and it depends on your Price Plan..
  8. Click on “RUN”
  9. Results will be generated and displayed on-the-fly
  10. After the calculation is finished, the hits will be ranked by the last workflow step (if you did not add new steps to the template workflow, they will be rank ordered by the docking scores)
  11. Check the predicted binding mode of the best hits by clicking on “VISUALIZE POSE”. You can take a closer look to the binding site and turn on surfaces with the “proteinsurface” button. Polar regions are colored red.
  12. If there is information available on critical amino acids of your target that participate in ligand binding, check if the hit forms interactions with those residues.
  13. You can request quote for any of the hits by clicking on the orange “QUOTE” buttons next to them. You can request quote for all hits in the output collection by clicking on the orange “QUOTE” button in the top right corner. Alternatively, you can select only the most interesting hits by using the checkboxes on the left and add them into a new or an already existing collection (“ADD TO” button). After that you can go to “COLLECTIONS”, open your created collection and click on the orange “QUOTE” button in the top right corner.

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