Chemomics is an interdisciplinary study using approaches from chemoinformatics,bioinformatics,synthetic chemistry,and other related disciplines.Biological systems make natural products from endogenous small molecules (natural product building blocks) through a sequence of enzyme catalytic reactions.For each reaction,the natural product building blocks may contribute a group of atoms to the target natural product.We describe this group of atoms as a chemoyl.A chemome is the complete set of chemoyls in an organism.Chemomics studies chemomes and the principles of natural product syntheses and evolutions.Driven by survival and reproductive demands,biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes;this results in biological and chemical diversity.In recent years,it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening.Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems,and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening.This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.
Human intestinal carboxyl esterase(hiCE)is a drug target for ameliorating irinotecan-induced diarrhea.By reducing irinotecaninduced diarrhea,hiCE inhibitors can improve the anti-cancer efficacy of irinotecan.To find effective hiCE inhibitors,a new virtual screening protocol that combines pharmacophore models derived from the hiCE structure and its ligands has been proposed.The hiCE structure has been constructed through homology techniques using hCES1’s crystal structure.The hiCE structure was optimized via molecular dynamics simulations with the most known active hiCE inhibitors docked into the structure.An optimized pharmacophore,derived from the receptor,was then generated.A ligand-based pharmacophore was also generated from a larger set of known hiCE inhibitors.The final hiCE inhibitor predictions were based upon the virtual screening hits from both ligand-based and receptor-based pharmacophore models.The hit rates from the ligand-based and receptor-based pharmacophore models are 88% and 86%,respectively.The final hit rate is 94%.The two models are highly consistent with one another(85%).This proves that both models are reliable.
