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.
J Chem Inf Model. 2013 Feb 25;53(2):279-92. doi: 10.1021/ci3002974. Epub 2013 Jan 24.
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.
引入蛋白质环境的化学等价性概念，作为化学片段生物等价性的补充性质。如果两个化学片段可以结合到相同的蛋白质环境中，则认为它们具有生物等价性；同样地，如果两个蛋白质环境可以与相同的化学片段相互作用，则认为它们具有化学等价性。目前，用于蛋白质-配体复合物的晶体结构越来越多，这为鉴定蛋白质环境之间的化学等价性关系提供了依据。结果表明，仅使用酶结构中存在的化学等价性环境，就可以恢复核受体结构中原配体中化学片段的正确位置和取向。提供了化学等价性在基于片段的药物发现中的潜在应用实例。
