usecases
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- | ====== Typical use cases of mcule ====== | + | ====== Typical use cases of Mcule ====== |
- | **[[ordsingle|Ordering a single compounds >> | + | **__[[ordsingle|Ordering a single compounds >>]]__** |
- | ==== Ordering a list of compounds from mcule ID list ==== | + | |
- | 1. Go to **[[http:// | + | **__[[ordmculelist|Ordering a list of compounds from mcule ID list >>]]__** |
- | 2. Paste your mcule ID list | + | **__[[ordlist|Ordering a list of compounds >> |
- | 3. Optionally you can add a **" | + | **__[[ordancat|Order analogs from catalogs (hit expansion) >> |
- | 4. Click on **" | + | **__[[usecasedownload|Download the Mcule database and come back for ordering >> |
- | 5. If your compounds were found, click on the orange | + | **__[[usecaseprefilter|Prefilter the Mcule database (design a screening library) >> |
- | 6. Fill out the quote form | + | **__[[usecasedownloadsubset|Download a subset of the Mcule database >> |
- | 7. Click on either **" | + | **__[[inhouseext|Extend your in-house compound deck >>]]__** |
- | ==== Ordering a list of compounds ==== | + | **__[[opthitlead|Optimize hits and leads >> |
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your query in SMILES, mcule ID, InChI or SDF formats (use the tabs on the left to **" | ||
- | |||
- | 3. Click on **" | ||
- | |||
- | 4. If your compounds were found, click on the orange **" | ||
- | |||
- | 5. Fill out the quote form | ||
- | |||
- | 6. Click on either **" | ||
- | |||
- | ==== Order analogs from catalogs (hit expansion) ==== | ||
- | |||
- | [[http:// | ||
- | |||
- | == A) Search close analogs for a single hit == | ||
- | |||
- | If you have a single hit and want to search and order its close analogs, follow these steps: | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your query (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 3. If you want to keep a particular substructure in all resulting analogs, modify your query accordingly (delete unnecessary parts) and select **" | ||
- | |||
- | 4. If you simply want the overall most similar analogs of your compound, select **" | ||
- | |||
- | 5. Click on **" | ||
- | |||
- | 6. After the search was finished and the most similar compounds were displayed, click on the orange **" | ||
- | |||
- | 7. Fill out the quote form | ||
- | |||
- | 8. Click on either **" | ||
- | |||
- | |||
- | == B) Search analogs for multiple hits by a single search == | ||
- | |||
- | If you have multiple hits containing common structural elements (e.g. multiple analogs of the same scaffold), it make sense to include all your hits in a single search as multiple queries. | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your queries in SMILES, mcule ID, InChI or SDF formats (use the tabs on the left to **" | ||
- | |||
- | 3. You can set the similarity **" | ||
- | |||
- | 4. Under **" | ||
- | |||
- | 5. Click on **" | ||
- | |||
- | 6. After the search was finished and the most similar compounds were displayed, click on the orange **" | ||
- | |||
- | 7. Fill out the quote form | ||
- | |||
- | 8. Click on either **" | ||
- | |||
- | == C) Search analogs for multiple hits (one hit at a time) == | ||
- | |||
- | If your hits are from fairly different scaffolds, it might make more sense to run separate similarity searches on each of them, merge the results into a single compound collection, and request a quote for the merged collection. | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your first query (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 3. If you want to keep a particular substructure in all resulting analogs, modify your query accordingly (delete unnecessary parts) and select **" | ||
- | |||
- | 4. If you simply want the overall most similar analogs of your compound, select **" | ||
- | |||
- | 5. Click on **" | ||
- | |||
- | 6. Repeat steps 1-5 for all your hits | ||
- | |||
- | 7. Go to **[[http:// | ||
- | |||
- | 8. You can select your most recent collections (results of your analog searches) and click on **" | ||
- | |||
- | 9. Alternatively, | ||
- | |||
- | 10. Go to the final collection that contains the selected analogs you would like to order and click on the orange **" | ||
- | |||
- | 11. Fill out the quote form | ||
- | |||
- | 12. Click on either **" | ||
- | |||
- | == D) Search for more diverse analogs of a single hit == | ||
- | |||
- | If you are looking for compounds with similar pharmacophore properties but more structural diversity you can use **[[http:// | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Depending on your **[[http:// | ||
- | |||
- | 3. Specify your query (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 4. Click on **" | ||
- | |||
- | 5. After the results are displayed you can visualize the similarity between the query and each identified analog by clicking on the **" | ||
- | |||
- | 6. To request a quote for any particular analog, you can click on the orange **" | ||
- | |||
- | 7. Fill out the quote form | ||
- | |||
- | 8. Click on either **" | ||
- | ==== Download the Mcule database and come back for ordering ==== | ||
- | |||
- | 1. You can download the Mcule database from **[[http:// | ||
- | |||
- | 2. If you would like to download only a subset of the Mcule database, you can **[[http:// | ||
- | |||
- | 3. After you processed the database in-house, you can come back and request a quote for a list of Mcule IDs: | ||
- | |||
- | 4. Go to **[[http:// | ||
- | |||
- | 5. Paste your Mcule ID list | ||
- | |||
- | 6. Optionally you can add a **" | ||
- | |||
- | 7. Click on **" | ||
- | |||
- | 8. If your compounds were found, click on the orange **" | ||
- | |||
- | 9. Fill out the quote form | ||
- | |||
- | 10. Click on either **" | ||
- | |||
- | ==== Prefilter the Mcule database (design a screening library) ==== | ||
- | |||
- | 1. You can start with our **[[http:// | ||
- | |||
- | 2. You can make adjustments to that template or build **[[http:// | ||
- | |||
- | 3. You might run your workflow on all **[[purchasable|Purchasable compounds]]** or choose any other molecule collections as input. | ||
- | |||
- | 4. In the workflow you can include various filters. For example, a reasonable prefiltering workflow might include **[[|Basic-]]** or **[[|Advanced Property filter]]**, **[[smartsquery|SMARTS filter]]**, **[[sampler|Sampler]]**, | ||
- | |||
- | 5. Optionally you can give a **" | ||
- | |||
- | 6. Click on **" | ||
- | |||
- | 7. After the search was finished, you can click on the **" | ||
- | |||
- | ==== Download a subset of the Mcule database ==== | ||
- | |||
- | 1. You can create custom subsets of the Mcule database by running searches in **[[http:// | ||
- | |||
- | 2. All your search results (outputs of searches in **[[http:// | ||
- | |||
- | 3. You can select any of your collections, | ||
- | |||
- | |||
- | ==== Extend your in-house compound deck ==== | ||
- | |||
- | The Mcule database contains millions of **[[purchasable|Purchasable compounds]]** providing a great pool of compounds to extend your existing in-house library. You can prefilter the Mcule database based on your own criteria, export it, select the interesting compounds in-house and **[[http:// | ||
- | ==== Optimize hits and leads ==== | ||
- | |||
- | [[http:// | ||
- | |||
- | Mcule offers a continuously growing set of intuitive, easy-to-use modeling applications specifically designed to evaluate and generate ideas in the hit/lead optimization process. | ||
- | |||
- | == A) Optimize binding affinity and selectivity with 1-Click Docking == | ||
- | |||
- | Molecular docking simulations predict the binding orientation and affinity of a ligand to a target. | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 3. Select or upload a target | ||
- | |||
- | 4. Click on **" | ||
- | |||
- | 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 **" | ||
- | |||
- | 6. Go back and draw a slightly modified version of your hit/lead | ||
- | |||
- | 7. Click on **" | ||
- | |||
- | 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 (**" | ||
- | |||
- | 10. Continue testing new ideas and improve the docking scores. You can also run other Lead Optimization tools, such as **[[http:// | ||
- | |||
- | 11. You can check your previous 1-Click Docking results and queries **[[http:// | ||
- | |||
- | 12. Additionally, | ||
- | |||
- | == B) Generate new ideas and eliminate problematic parts by 1-Click Scaffold Hop == | ||
- | |||
- | Scaffold hopping is about finding novel active ligands structurally different from a reference ligand (query). Scaffold hopping can be particularly useful during lead optimization to generate new ideas or to eliminate particular parts of your hit/lead to fix IP, toxicity, selectivity or pharmacokinetic issues. 1-Click Scaffold Hop is searching different subsets of **[[purchasable|Purchasable compounds]]** | ||
- | that might be structurally different but share pharmacophore properties with those of the query. | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Depending on your **[[http:// | ||
- | |||
- | 3. Specify your existing hit / lead / reference ligand (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 4. Click on **" | ||
- | |||
- | 5. After the calculation finishes you can find a number of diverse scaffolds that have similar pharmacophore properties as your query | ||
- | |||
- | 6. Click on **" | ||
- | |||
- | 7. Remember that all displayed hits are purchasable. To order any of them, click on the orange **" | ||
- | |||
- | 8. You can check your previous 1-Click Scaffold Hop results and queries **[[http:// | ||
- | |||
- | 9. You can use the other Lead Optimization tools, such as **[[http:// | ||
- | |||
- | == C) Property calculator == | ||
- | |||
- | ADMET properties heavily depend on physicochemical properties. For example, high logP (> 5) and molecular weight (> 500 g/mol) are typically associated with unsuitable ADMET profile. Property calculator creates a physicochemical property profile for your compound in seconds. You can reject compounds with unsuitable logP, insufficient number of H-bond acceptors/ | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 3. Click on **" | ||
- | |||
- | 4. Check the calculated properties of your original hit/lead. Depending on your **[[http:// | ||
- | |||
- | 5. Go back and draw a slightly modified version of your hit/lead | ||
- | |||
- | 6. Click on **" | ||
- | |||
- | 7. After the calculation finishes you can check the individual properties and see if problematic properties got improved due to your modification in the hit/lead structure | ||
- | |||
- | 8. You can use the other Lead Optimization tools, such as **[[http:// | ||
- | |||
- | == D) Toxicity checker == | ||
- | |||
- | Certain structural elements of a molecule can be responsible for toxicity. In fact, some substructural motifs occur more frequently in toxic compounds than in non-toxic ones. It therefore makes sense to eliminate such structural motifs from hits/leads as early as possible. Toxicity Checker is based on more than 100 toxic and promiscuous scaffolds. It displays an alert, when such a motif is found, and it displays the incriminated part of the molecule. | ||
- | |||
- | 1. Go to **[[http:// | ||
- | |||
- | 2. Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey) | ||
- | |||
- | 3. Click on **" | ||
- | |||
- | 4. If the compound contains any potential toxic substructure, | ||
- | |||
- | 5. Go back and try to modify the problematic motif of your hit/lead | ||
- | |||
- | 6. Click on **" | ||
- | |||
- | 7. Continue the modifications, | ||
- | |||
- | 8. You can use the other Lead Optimization tools, such as **[[http:// | ||
==== Hit identification ==== | ==== Hit identification ==== | ||
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sampler | sampler | ||
+ | **__[[usecases|Go back to use cases >> | ||
== B) Ligand-based virtual screen == | == B) Ligand-based virtual screen == | ||
Ligand-based virtual screening does not utilize the 3D structure of the target when searching for new hits. Instead, it is based on the structure of a reference ligand (endogenous ligand, known inhibitor, etc.) that binds to a target and/or exhibits some beneficial effect. In ligand-based virtual screening, compounds are typically ranked based on the similarity to the reference ligand (query). | Ligand-based virtual screening does not utilize the 3D structure of the target when searching for new hits. Instead, it is based on the structure of a reference ligand (endogenous ligand, known inhibitor, etc.) that binds to a target and/or exhibits some beneficial effect. In ligand-based virtual screening, compounds are typically ranked based on the similarity to the reference ligand (query). | ||
+ | |||
+ | **__[[usecases|Go back to use cases >> |
usecases.txt · Last modified: 2014/01/01 15:23 by flack