George recently attended the inaugural Schaap Chemistry Symposium hosted by Hope College in Holland, MI. He attended to present his research on the development of a virtual screening platform for the prediction of HLA-B*57:01 mediated adverse drug reactions (DOI: 10.1186/s13321-017-0202-6). A recount of the trip can be found here.
HLA triggered adverse drug reactions: Challenges and opportunities for molecular modeling
George Van Den Driessche, Denis Fourches*
*Department of Chemistry, Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA
When a patient is administered a drug, there is the possibility that the drug may cause mild to severe side effects known as an adverse drug reaction (ADR). Idiosyncratic, or immune-based, ADRs are commonly triggered when a drug binds with a human leukocyte antigen (HLA) protein. Some well-known ADRs include abacavir hypersensitivity syndrome (AHS, HLA-B*57:01-abacavir), drug induced liver injury (DILI, HLA-B*57:01-pazopanib), and Steven-Johnson Syndrome (SJS, HLA-B*15:02-carbamezapine). Correlating ADRs with the HLA protein is extremely difficult due to varying frequency of protein occurrence in the population, numerous HLA variants (>15,000), and HLA-drug binding promiscuity. As such, the development of tools that accurately and efficiently forecast HLA-drug interactions is imperative for patient safety and the field of Precision Medicine. This presentation will discuss the application of cheminformatics to forecast HLA-B*57:01 liable compounds by developing a virtual screening platform, screening the DrugBank database, and exploring HLA-drug molecular interactions using molecular dynamics.