This is an old revision of the document!
In case you cannot search / screen the full Mcule database, you may consider using some smaller, representative subsets thereof prefiltered by physicochemical properties and diversity. Structurally diverse subsets representing the drug-like (rule-of-5) and fragment (rule-of-3) chemical space can be accessed as described below.
The subsets can be
For the drug-like and fragment-like subsets the rule of 5 and rule of 3 rules were applied, allowing one violation. Additionally, we used a few more rules:
We used these rules to leave out more “strange compounds” which may be included more likely in the diverse sets as they differ from the regular compounds.
The Mcule database contains ~5.7M stock compounds and ~30.3M virtual compounds. Diversity selection was carried out in a way to prefer the stock compounds over the virtual ones. As a result, the chemical space is represented by stock compounds where possible. More over, the downloadable files contains the compounds in diversity order i.e. the first N compounds represent the most dissimilar N compounds, so you can choose yourself the number of compounds to represent the whole Ro3 and Ro5 subsets.
Structural similarity was measured by Tanimoto coefficient (TC) between FP2 linear fingerprints generated by OpenBabel. The combinations of the following algorithms were applied to extract the most dissimilar subsets:
In sphere exclusion we used the stock compounds first as “centers” for the elimination of redundant compounds, and we retained the stock compounds during the stepwise elimination.
To speed up the selection, we used sphere exclusion in case of the Ro5 subsets with TC=0.8 to pass at most 3M compounds for stepwise elminiation. Then, the following subsets were saved:
|Subset name||Input||Property filter||Diversity||Subset size|
|Mcule Purchasable (In Stock Ro5 Diverse 1M)||Stock compounds||rule-of-5, max 1 violation||top diverse 1M, max TC: 0.8||1,000,000|
|Mcule Purchasable (In Stock Ro5 Diverse 350K)||Stock compounds||rule-of-5 (max 1 violation)||Top diverse 350K, max TC:0.7||350,000|
|Mcule Purchasable (In Stock Ro3)||Stock compounds||rule-of-3 (max 1 violation)||-||154,238|
|Mcule Purchasable (In Stock Ro3 Diverse 50K)||Stock compounds||rule-of-3 (max 1 violation)||Top diverse 50K, max TC: 0.8||50,000|
|Mcule Purchasable (In Stock & Virtual Ro3)||Stock compounds + virtual compounds||rule-of-3 (max 1 violation)||-||789,907|
|Mcule Purchasable (In Stock & Virtual Ro3 Diverse 70K)||Stock compounds + virtual compounds||rule-of-3 (max 1 violation)||Top diverse 70K, max TC: 0.8||70,000|