Informatics investigations into HLA-mediated adverse drug reactions

Ramsbottom, Kerry ORCID: 0000-0002-7432-9293 (2020) Informatics investigations into HLA-mediated adverse drug reactions PhD thesis, University of Liverpool.

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Abstract

Adverse drug reactions have been associated with multiple alleles of human leukocyte antigens (HLA) genes for different drugs in different populations. In practice, this means an individual carrying a particular HLA allele has an increased risk of developing an adverse reaction to a certain drug. Computational methods, in particular molecular docking, can be used to improve understanding of the mechanisms involved in these HLA-mediated adverse drug reactions through predictions of the preferred binding positions and affinity between the drugs and their unintended HLA targets. Furthering understanding of these reactions may enable us to predict the risk of these adverse events in a wider range of scenarios, such as low frequency HLA alleles, and thus lead to preventative measures being implemented. The molecular docking techniques commonly used to investigate these associations were first critically assessed. The performance of four different docking software packages were compared using the widely studied abacavir example, for which a crystal structure of the drug bound in complex with the risk allele exists, for benchmarking the techniques. The outcomes of these investigations were then used to investigate ... (continues)

Item Type:	Thesis (PhD)
Divisions:	Faculty of Health & Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	08 Apr 2020 14:27
Last Modified:	08 Feb 2025 02:04
DOI:	10.17638/03074372
Supervisors:	Jones, Andrew R ORCID: 0000-0001-6118-9327 Rigden, Daniel J ORCID: 0000-0002-7565-8937 Carr, Daniel F
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3074372
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