title: Chemoisosterism in the proteome.
abstract: The concept of chemoisosterism of protein environments is introduced as the complementary property to bioisosterism of chemical fragments. In the same way that two chemical fragments are considered bioisosteric if they can bind to the same protein environment, two protein environments will be considered chemoisosteric if they can interact with the same chemical fragment. The basis for the identification of chemoisosteric relationships among protein environments was the increasing amount of crystal structures available currently for protein-ligand complexes. It is shown that one can recover the right location and orientation of chemical fragments constituting the native ligand in a nuclear receptor structure by using only chemoisosteric environments present in enzyme structures. Examples of the potential applicability of chemoisosterism in fragment-based drug discovery are provided.
authors: Chemogenomics Laboratory, Research Programme on Biomedical Informatics (GRIB), IMIM Hospital del Mar Research Institute and University Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors: Xavier
authors: X
authors: Jalencas
authors: Jordi
authors: J
authors: Mestres
mesh_terms: D030562:Databases, Protein; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D020543:Proteome