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Molecular docking simulations predict the binding orientation and affinity of a ligand to a target. With 1-Click Docking you can run sequential docking simulations online, and optimize the binding affinity of your ligand. A step-by-step description is provided here for this use case. If you would like to get more information about the 1-Click Docking application, please click here.
1. Go to LEAD OPTIMIZATION / 1-CLICK DOCKING
2. Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILES or InChI)
3. Select or upload a target
4. Click on “DOCK”
5. After the docking calculation finishes you can check the estimated binding affinity (docking score - more negative means higher affinity) and visualize the critical interactions that have been formed between your ligand and the target by clicking on “VISUALIZE POSE”.
6. Go back and draw a slightly modified version of your hit/lead
7. Click on “DOCK”
8. After the docking calculation finishes you can compare the docking scores and the formed interactions of the modified molecule and those of the original hit/lead.
9. To get an idea where the compound can be further adjusted, take a closer look at the binding mode (“VISUALIZE POSE”). Turn on the “proteinsurface” feature to see where is additional space for optimization. Red colored surface parts indicate polar regions.
10. Continue testing new ideas and improve the docking scores. You can also run other Lead Optimization tools, such as Property Calculator and Toxicity Checker to make sure other properties of the ligand are not impaired. In fact, try to improve multiple things simultaneously by checking all properties of the same idea.
12. Additionally, you can take a step forward and calculate the binding affinity to off-targets, you don't want your ligand to bind to. For example to design a subtype specific inhibitor, you might need high binding affinity to subtype “A”, but low affinity to subtype “B”. For this select other targets and dock your ligand again.