Abstract：
:Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these multitarget interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover the complex relationships between them. Here, we introduce an approach which is able to relate complex drug-protein interaction profiles with effect profiles. Structural data and registered effect profiles of all small-molecule drugs were collected, and interactions to a series of nontarget protein binding sites of each drug were calculated. Statistical analyses confirmed a close relationship between the studied 177 major effect categories and interaction profiles of ca. 1200 FDA-approved small-molecule drugs. On the basis of this relationship, the effect profiles of drugs were revealed in their entirety, and hitherto uncovered effects could be predicted in a systematic manner. Our results show that the prediction power is independent of the composition of the protein set used for interaction profile generation.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Simon Z,Peragovics A,Vigh-Smeller M,Csukly G,Tombor L,Yang Z,Zahoránszky-Kohalmi G,Végner L,Jelinek B,Hári P,Hetényi C,Bitter I,Czobor P,Málnási-Csizmadia Adoi
10.1021/ci2002022subject
Has Abstractpub_date
2012-01-23 00:00:00pages
134-45issue
1eissn
1549-9596issn
1549-960Xjournal_volume
52pub_type
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