Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

Hu, Le-Le; Chen, Chen; Huang, Tao; Cai, Yu-Dong; Chou, Kuo-Chen

As stated in the Method section, the interactive compounds derived from STITCH tend to participate in the same metabolic pathways. For example, Table 3 lists the interactions of dihydrouracil with other compounds. Among the 32 interactive compounds, most of them appear in ''metabolism of cofactors and vitamins'' or ''metabolism of other amino acids'' or ''nucleotide metabolism'' pathway class (cf. Table 1 ) just like dihydrouracil. Dihydrouracil and uracil participate in pyrimidine metabolism pathway (belong to ''nucleotide metabolism''), where 5,6-dihydrouracil and NADP+ are catalyzed by dihydropyrimidine dehydrogenase (DPD) to form uracil and NADPH+H+ [14, 27] . They are also co-mentioned in many PubMed Abstracts such as [28, 29, 30, 31, 32, 33, 34, 35, 36, 37] . Another two interactive compounds -dihydrouracil and dihydrothymine share a very similar structure, the only difference is that dihydrothymine has a methyl at the 5th position of the hexatomic ring while dihydrouracil has not [38] . According to the prediction criteria, when dihydrouracil was treated as a query compound, the first three order predicted metabolic pathways that it participates in are ''nucleotide metabolism'', ''metabolism of cofactors and vitamins'' and ''metabolism of other amino acids'', respectively, which are consistent with the true metabolic pathways that it is involved in.