Pharmacogenomics from a Protein Structure Perspective
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The human genome comprises approximately 20,000 protein-coding genes and over 900 million variants according to dbSNP. Systematic understanding of the impact of genomic alterations in humans is critical for the development of effective medicines. However, it is simply not feasible to study every single variant in detail. This challenge extends to the analysis of how pharmacogenes are affected by genetic polymorphisms, as it is impossible to study the impact of every individual single nucleotide polymorphisms/variations (SNPs/SNVs) of pharmacogenes in human clinical trials. Yet, understanding drug metabolism and pharmacokinetics is crucial for assessing drug efficacy and safety. To minimize harmful side effects from drugs while maximizing their therapeutic effectiveness in each patient or group of patients, we would need to understand the effects of population specific SNPs in pharmacogenes and drug-enzyme interactions. To date the effect of non-synonymous SNPs, more specifically missense mutations, at the protein level is poorly studied in pharmacogenomics research. We previously proposed a post-hoc analysis approach of molecular dynamics (MD) simulations using dynamic residue network (DRN) analysis to consider the dynamic nature of functional proteins and protein-drug complexes and to probe the impact of mutations and their allosteric effects. This talk will discuss the computational approaches and tools that we have developed over the years with applications to pharmacogenomics.
Özlem Tastan Bishop
Özlem is full Professor in structural bioinformatics at Rhodes University, South Africa and distinguished adjunct Professor at Saveetha University, Chennai, India.
She received her BSc degree in Physics from Boğaziçi University, Istanbul, Turkey. Then she moved to the Department of Molecular Biology and Genetics at the same University for her MSc degree. She obtained her PhD from Max-Planck Institute for Molecular Genetics and Free University, Berlin, Germany in 2003. While doing her PhD, Özlem became interested in structural biology, and during her postdoctoral positions (Texas University, USA; University of Western Cape and University of Pretoria, South Africa) she gained experience in structural bioinformatics as well as structural biology.
In 2009, Özlem took up an academic position at Rhodes University, South Africa. She established the Research Unit in Bioinformatics (RUBi) in 2013. She has graduated 25 PhD and 38 MSc students since she joined Rhodes University. She received Rhodes University Internationalization award for 2018; Rhodes University Vice Chancellor’s Distinguished Senior Research award for 2020 and South African Society for Bioinformatics (SASBi) Silver Award, 2022.
She serves on the Editorial Board for PLOS Computational Biology, PLOS One and Frontiers in Molecular Biosciences and Frontiers in Applied Mathematics and Statistics, Biological Modeling and Simulation Section, and she is an Advisory Board member of F1000Research Bioinformatics Gateway. Özlem’s broad research interest is structural bioinformatics and its applications to drug design and development. Her recent interest is in the allosteric mechanisms of proteins and understanding the effects of nonsynonymous single nucleotide variations on protein structure and function in the context of drug resistance and drug metabolism. She has published roughly 100 research articles.