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Drug Discov Today. 2014 Sep;19(9):1353-63. doi: 10.1016/j.drudis.2014.06.018. Epub 2014 Jun 26.

CANDO and the infinite drug discovery frontier.

Author information

1
University of Washington, Department of Bioengineering, Seattle, WA 98109, United States.
2
University of Washington, Department of Microbiology, Seattle, WA 98109, United States; University of California, San Francisco, Diabetes Center, San Francisco, CA 94143, United States.
3
University of Washington, Department of Microbiology, Seattle, WA 98109, United States.
4
University of California, School of Medicine, San Francisco, CA 94143, United States.
5
Georgia Institute of Technology, Center for the Study of Systems Biology, Atlanta, GA 30318, United States.
6
Molecular Biophysics Unit, Indian Institute of Science Bangalore, 560012, India.
7
University of Washington, Department of Microbiology, Seattle, WA 98109, United States. Electronic address: ram@compbio.org.

Abstract

The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound-proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12-25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 'high value' predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering.

PMID:
24980786
PMCID:
PMC4167471
DOI:
10.1016/j.drudis.2014.06.018
[Indexed for MEDLINE]
Free PMC Article

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