Computational Toxicology

Chapter 12HLA-Mediated Adverse Drug Reactions: Challenges and Opportunities for Predictive Molecular Modeling

George van Den Driessche and Denis Fourches

Department of Chemistry, Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA

Chapter Menu

1. Introduction
2. Human Leukocyte Antigens
3. Structure-Based Molecular Docking to Study HLA-Mediated ADRs
4. Perspectives

12.1 Introduction

Adverse Drug Reactions (ADRs) are mild-to-serious undesired effects a patient can undergo after taking a particular medication. ADRs can even be life threatening for certain subpopulations of patients. Overall, ADRs present a major financial burden to the US healthcare system [1]. One important challenge for accurately monitoring both the occurrences and financial burdens associated with ADRs is mainly the lack of a cohesive definition used to track such events [2]. According to the FDA Adverse Event Reporting System (FAERS), there were over 1.2 million adverse events reported in 2014 compared to only 400,000 cases in 2006 [3]. For all the aforementioned reasons, there is a strong need to develop computational models that could accurately predict a drug's likelihood of causing ADR. In fact, models reliably predicting such ADR for a subpopulation of patients are especially in high demand for future precision medicine protocols.

There are two main different types of ADRs referred to as Type I and Type II [4, 5]. Type I ADRs are predictable pharmacological events induced by a drug, ...