Comprehensive prediction of drug protein interactions and side effects for the human proteome
Identifying unexpected drug protein interactions is crucial for drug repurposing. We develop a comprehensive proteome scale approach that predicts human protein targets and side effects of drugs. For drug protein interaction prediction, FINDSITEcomb, whose average precision is ~30% and recall ~27% is employed. For side effect prediction, a new method is developed with a precision of ~57% and a recall of ~24% Our predictions show that drugs are quite promiscuous, with the average (median) number of human targets per drug of 329 (38) while a given protein interacts with 57 drugs. The result implies that drug side effects are inevitable and existing drugs may be useful for repurposing, with only ~1,000 human proteins likely causing serious side effects. A killing index derived from serious side effects has a strong correlation with FDA approved drugs being withdrawn. Therefore, it provides a pre filter for new drug development. The methodology is free to the academic community on the DR. PRODIS (DRugome, PROteome, and DISeasome) webserver at http:/cssb.biology.gatech.edu/dr.prodis/ DR. PRODIS provides protein targets of drugs, drugs for a given protein target, associated diseases and side effects of drugs, as well as an interface for the virtual target screening of new compounds.
Scientific reports