Privileged Pfam-A domains mediate small molecule binding
We query the ChEMBL database for measured interactions of small molecules with single domain proteins containing a given domain. The requirements for a measurement to be counted as evidence are then the following:
The intial implementation built on a slightly different set of requirements, listed below. The most profound difference is that it set the threshold at 50 μM. Upon revisiting activities in the range between 10 and 50 μM, we found that they mostly represented unusual assay formats or ligands that do not fit in well with classical definitions of small molecules.
Evidence for small molecule binding to 243 Pfam-A domains is listed below.
The catalogue of Pfam-A domains which are known to mediate small molecule binding can be downloaded in whole as valid_domains.download expand table legend
|entry_id||unique identifier for each row|
|domain_name||name of the Pfam-A domain|
|timestamp||time of last curation|
|submitter||user who submitted last curation decision|
The catalogue of valid Pfam-A domains is subject to revision. For example, if new data in the literature suggests that a given domain mediates small molecule binding, it can be added to the PPDMs list of domains under review. In the next cycle of curations, it can be included in the main catalogue and will be projected onto proteins that are associated with eligible binding assays. Similarly, a domain that is currently listed in the catalogue can be shortlisted for removal if evidence for small molecule binding turns out to be insubstantial.
All domains that are currently under review are listed below 4.
|Aph-1||No ligands were found associated with Aph-1 containing single domain proteins in chembl_17.||fak||March 17, 2014, 4:12 p.m.|
|Telo_bind||Telo_bind was renamed to POT1 in Pfam-A||fak||March 17, 2014, 4:12 p.m.|
|Peptidase_M84||Peptidase_M84 was renamed to Reprolysin_5 in newer Pfam release||fak||March 17, 2014, 4:12 p.m.|
|Glyco_hydro_14||The most potent of 6 recorded ligands showed IC50 of 65 micro-molar.||fak||March 17, 2014, 4:12 p.m.|