So-called in silico meaning "virtual"—screens were utilized to search extensive small-molecule chemical libraries for candidates predicted to bind to a region of a three-dimensional structure of a given macromolecule, such as the active site of an enzyme.
We describe here an improved, extensive small-molecule chemical compound library screen for p53 pathway activation in a human cancer cell line devised to identify hits with potent antitumor activity.
This contrasts with an extensive literature documenting that small molecule inhibitors of other RTKs such as epidermal growth factor receptor strongly inhibit ligand-induced activation of ERK and Akt.
Where extensive data on small molecules are presented in chemical reports, structures should be annotated according to compound identifiers in the authoritative database PubChem.
However, we now know that small molecule drugs have extensive polypharmacologies, which may contribute to their clinical efficacy, or adverse effects or may provide insight into new repositioning opportunities.
[In IMP-1 and CcrA, Trp59 87), otherwise conserved in B1 MBLs, is replaced by a phenylalanine residue which also contributes to the hydrophobic pocket involved in inhibitor binding.] Thiomandelate, a relatively small molecule, makes less extensive interactions with residues in the β3 β4 loop compared with many of the other inhibitors whose binding to MBLs has been studied crystallographically.
Finally, for potential small molecule targets, we mined extensive databases of existing small molecule inhibitors and their targeting proteins.
Currently (as of April 3, 2014) there exist more than 72000 experimentally determined protein structures complexed with small molecule ligands, providing an extensive data resource on protein binding sites.
Of these, 18 belong to protein families for which extensive 3D structural information is available, including bound small molecule ligands and drugs.
