How are structures in the Probes and Drugs portal curated?
The structures are uploaded to the database in their original form as provided by a data source. The main reason is that we want to show the actual situation in the field of bioactive compounds. Another reason is that very often it is very hard to assess the right stereochemical form of a compound or e.g., the active form of a compound (compound X its salt).
How were the compound sets in the Probes & Drugs Portal selected?
There was no special screening process concerning the selection of compound sets currently contained in the Probes and Drugs portal. The sets were selected according to their availability, and popularity within scientific community. Not all compound sets we wanted to incorporate into our database could be incorporated because of their availability or license restrictions. The Probes and Drugs portal is open to incorporation of new compound sets.
How is a compound tagged as a probe?
A compound is tagged as a probe when this information is specified by the data vendor and it is not tagged as obsolete at the same time. Every compound from probe sets Chemical Probes.org, SGC probes, MLP probes and Nature Chemical Biology probes is tagged as a probe; also compounds tagged as probes in Informer set 2.0 and MLSMR Probes+ are tagged as a probe on the portal.
How is a compound tagged as a drug?
A compound is tagged as a drug when it belongs to one of the drug sets (DrugBank, DrugCentral, NIH Approved oncology drugs, ChEMBL Approved Drugs) or when it is classified as a drug by one of the external data sources (currently ChEMBL and Guide to PHARMACOLOGY).
What is the difference between original and standardized compound?
Original compound is a compound extracted from a source file without any changes. On the other side, standardized compound is a compound created from an original compound by removing stereochemistry and salts/solvents. That means that for each original compound there is exactly one standardized compound, but there can be more original compounds for one standardized compound (e.g., when the original compounds have different stereochemistry or one is in a form of a salt).
Standardized compound not only joins probably the same original compounds in a different form (or maybe inaccurate form), but also joins all data associated with these compounds. There can actually be more data associated with a standardized compound than is the combination of its all original compounds. This can happen when data extracted from external sources are associated with a standardized compound structure (its inchikey) and not any of its original structures.
For example, there are five original compounds for the well-established anti-mitotic chemotherapy drug docetaxel because of their different forms and only one of them is actually tagged as a drug. When standardized, all of these compounds with their data are merged in one standardized compound.
Why should I register at the Probes & Drugs portal?
Only when you are registered and logged in, you can create your own custom sets (more on custom sets here) which can be further used in new queries. There will also be more functions available only for registered users in the future.
What are custom sets?
Custom sets are arbitrary, user defined, compound sets intended to store advanced queries with possibility to manually add/remove single compounds.
Since custom sets are bound to a user, only registered and logged users can create them. First, a custom set has to be initialized in the Custom Sets tab. Once a custom set is created, single or multiple (batch) compounds can be added from the Compounds tab. Single by clicking on an arrow in a top right corner when hovering over a compound's image; multiple by clicking on the larger arrow on the right side of the second navigation tab. Compounds can be removed from a custom set only in a particular custom set view (Custom Sets > click on a custom set) using a cross icon. Again, both single and multiple compounds can be removed.
Currently, the maximum number of custom sets per user is limited to 5.
What is a structural alert?
Structural alert is a specific tag which should tell a user to be aware about a possible problematic behavior of a compound in the context of biological screening. It is associated either with a compound’s biological properties (e.g., non-selective or not sufficiently potent compound) or its structural features that may cause unwanted effects within an assay (e.g., non-specific reaction with a protein). Currently, three different types of structural alerts are integrated into the portal: Pan Assay Interference filters (PAINs), aggregators and obsolete compounds.
What is the Potency-Selectivity score?
The Potency-Selectivity score (PS score) combines together the information about the selectivity and potency of a compound on a particular target, based on available data. As such, it should serve as a simple metric representing the suitability of a compound to be used for the modulation of a target, either as a standalone indicator or in combination with the potency of a compound, which is often used exclusively.
Our PS score is highly inspired by the potency and selectivity parts of the Probe Miner probe-likeness score (you can read more about it here) and it is based on two factors: potency and selectivity.
The potency of a compound plays in this case a role of a weighing factor of the selectivity score. The potency weight is calculated from the median of all available activity values for a compound-target pair (only human targets are considered) and it's ranging from 0 to 1. The value is calculated as a linear normalization of median pActivity values between 5 (10 micromolar potency) and 10 (100 picomolar potency). All compounds with median pActivity value lower than 5 are considered to be inactive (weight 0) on a particular target, all values greater than 10 are equal to weight value 1.
The selectivity part of the PS score is based on two selectivity factors. First factor is a ratio of off-targets for which the potency of a compound is more than 10-fold selective and of all known off-targets.
The second factor quantifies in more detail the selectivity on a particular target and also distinguishes between compounds that have equal first factor but different number of known off-targets. The second factor is a ratio of a so-called Selectivity Information Richness (SIC) and of a number of not 10-fold selective off-targets plus one. The SIC is calculated as the sum of differences between the pActivity of the reference target and the pActivity of each off-target minus one.
The second factor is finally normalized within each target as we observe that different targets can have very different SIC ranges. Finally, the selectivity score is equal the sum of both selectivity factors divided by two.
Finally, the potency-selectivity score is equal to the selectivity score is multiplied (weighed) by the potency score.
What is a chemical space network?
Chemical space network (CSN) is a representation of chemical space in a form of a network where some of the displayed compounds/points (in extreme cases, all of them or none) are interconnected by edges (links) according to a defined molecular similarity threshold. Its default value on the P&D portal is set to 0.7, i.e., 70% similarity, but any number in range from 0.3 to 1 can be used.
Another parameter that influences the number of edges in the CSN is the number of maximum nearest neighbours (Max NN). Using this parameter, the maximum number of most similar compounds connected to a particular compound can be limited (even though there could be more meeting the similarity threshold parameter). In case any compound is already connected to its the maximum number of NNs, but also belongs to other compound's NNs (not already connected), then such pair is also connected together. In case you want to connect all compounds meeting the similarity threshold, leave the max NN parameter empty.
Which web browsers are recommended for the Probes & Drugs portal?
P&D portal is a complex web application that utilizes latest functionality integrated in HTML5 and CSS3 technologies. For that reason, using some of the older or not so common web browsers can lead to an unexpected appearance and behaviour of the portal. We recommend to use one of the following browsers with the specified or a newer version:
For smoothest user experience, we recommend to use Chrome.