Certain patients experience adverse drug reactions (ADR) after taking a particular medication. Immune-based idiosyncratic ADR are particularly difficult to predict, but they have been associated with drugs’ ability to bind with human leukocyte antigen (HLA) proteins. This presentation will discuss <i>(1)</i> the challenges for modeling HLA-drug complexes using current molecular modeling approaches, and <i>(2)</i> the numerous opportunities for modelers to develop new models and methods that forecast drugs’ potential to be HLA liable. As a case study, we will discuss the abacavir hypersensitivity syndrome (AHS) occurring when the antiviral drug abacavir binds with the human leukocyte antigen B*57:01 variant via an altered repertoire complex. Then, we will present the results of a virtual screening of the whole Drugbank library to identify hypothetical HLA-B*57:01 liable drugs. Finally, we will discuss the key perspectives of molecular modeling for HLA variants, including the use of molecular dynamics simulations to study and better understand the multibody HLA-drug-peptide complexes.

HLA-triggered adverse drug reactions: Challenges and opportunities for molecular modeling

253rd National Meeting (2017)

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