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usecase1cd [2013/10/10 18:08]
flack
usecase1cd [2013/12/02 23:25]
sanmark use order list
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 ====== Optimize binding affinity and selectivity with 1-Click Docking ====== ====== Optimize binding affinity and selectivity with 1-Click Docking ======
  
-Molecular docking simulations predict the binding orientation and affinity of a ligand to a target.+Molecular docking simulations predict the binding orientation and affinity of a ligand to a target. With [[1clickdocking|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 [[1clickdocking|1-Click Docking]] application,​ [[1clickdocking|please click here]].
  
-1. Go to **[[https://​mcule.com/​apps/​1-click-docking/​|LEAD OPTIMIZATION / 1-CLICK DOCKING]]** +  - Go to **[[https://​mcule.com/​apps/​1-click-docking/​|LEAD OPTIMIZATION / 1-CLICK DOCKING]]** 
- +  ​- ​Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILES ​or InChI) 
-2. Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILESInChI or InChIKey+  ​- ​Select or upload a target 
- +  ​- ​Click on **"​DOCK"​** 
-3. Select or upload a target +  ​- ​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"​**.  
- +  ​- ​Go back and draw a slightly modified version of your hit/lead 
-4. Click on **"​DOCK"​** +  ​- ​Click on **"​DOCK"​** 
- +  ​- ​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. 
-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"​**.  +  ​- ​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. 
- +  ​- ​Continue testing new ideas and improve the docking scores. You can also run other Lead Optimization tools, such as **[[https://​mcule.com/​apps/​property-calculator/​|Property Calculator]]** and **[[https://​mcule.com/​apps/​toxicity-checker/​|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. 
-6. Go back and draw a slightly modified version of your hit/lead +  ​- ​You can check your previous 1-Click Docking results and queries **[[http://​mcule.com/​apps/​1-click-docking/​history|HERE]]**. If you run out of storage, check the **[[http://​mcule.com/​pricing|Price Plans]]** to upgrade. 
- +  ​- ​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.
-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 **[[https://​mcule.com/​apps/​property-calculator/​|Property Calculator]]** and **[[https://​mcule.com/​apps/​toxicity-checker/​|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. +
- +
-11. You can check your previous 1-Click Docking results and queries **[[http://​mcule.com/​apps/​1-click-docking/​history|HERE]]**. If you run out of storage, check the **[[http://​mcule.com/​pricing|Price Plans]]** to upgrade. +
- +
-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.+
  
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usecase1cd.txt · Last modified: 2013/12/02 23:25 by sanmark