Physical Chemistry Seminar: S. Joshua Swamidass, Washington University
Physical Chemistry Seminar: Professor S. Joshua Swamidass, Washington University, Clark Center Room S360 (Host: Vijay Pande)
About the Seminar:
"Deep Learning the Metabolism and Subsequent Reactivity of Drugs"
http://swami.wustl.edu/bioreact
http://swami.wustl.edu/epoxidation-paper
Adverse drug reactions (ADRs) are dangerous and expensive. Idiosyncratic ADRs, especially rare and severe hypersensitivity-driven ADRs, are the leading cause of medicine withdrawal and termination of clinical development. At the same time, a large proportion of drugs are not associated with hypersensitivity driven ADRs, offering hope that new medicines could avoid them entirely with reliable predictors of risk. Hypersensitivity driven ADRs are caused by the formation of chemically reactive metabolites by metabolic enzymes. These reactive metabolites covalently attach to proteins to become immunogenic and provoke an ADR. Unfortunately, current computational and experimental approaches do not reliably identify drug candidates that form reactive metabolites. These approaches are limited because they inadequately model metabolism, which can both render toxic molecules safe and safe molecules toxic. To overcome this limitation, we have been building mathematical models of metabolism and reactivity. The models are constructed using Deep Learning: a machine-learning algorithm that quantitatively summarize the knowledge from thousands of published studies. Taken together, this approach is more accurately modeling the properties determining whether metabolism renders drugs toxic or safe.
About the Speaker: Dr. S. Joshua Swamidass MD PhD is an Assistant Professor in Laboratory and Genomic Medicine at Washington University in Saint Louis. Dr. Swamidass' group was recently funded by the NIH to computationally modeling the formation of reactive metabolites.. This effort is designed to identify the mechanism by which new drugs could be bioactivated so as to cause idiosyncratic hypersensitivity-driven drug reactions, an ongoing challenge in drug development. His CV can be found at http://swami.wustl.edu/swamidass_cv.pdf and website at http://swami.wustl.edu/.