title: Comprehensive prediction of drug-protein interactions and side effects for the human proteome.
abstract: 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, FINDSITE(comb), 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 A killing index derived from serious side effects has a strong correlation with FDA approved drugs being withdrawn.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.
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street, N.W., Atlanta, GA 30318.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street, N.W., Atlanta, GA 30318.
authors.forename: Mu
authors.initials: M
authors.lastname: Gao
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street, N.W., Atlanta, GA 30318.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D020543:Proteome
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins; D020543:Proteome