Charleen Don received her Master in biochemistry from Utrecht University, the Netherlands. Under the supervision of Prof. Alexandre Bonvin she completed her thesis entitled “Less is more: Integration of the MARTINI coarse grained model into HADDOCK”. After her studies, she gained research experience as intern at the Biomolecular Research Laboratory at the Paul Scherrer Institut CH, and as research assistant at the Laboratory of Physical Chemistry, ETH Zürich. In addition, she worked for a short period in the financial world. She has joined the Molecular Modeling group of PD Dr. Martin Smiesko in February 2017 as a PhD student. Her main project is focused on investigating pharmacogenetics of human cytochrome CYP2D6 using an integrative modeling approach. She published in several journals including WIREs, PlosOne and Journal of chemical information and modeling. 

OpenTox Euro 2019 talk: Cytochrome P450 2D6 as an anti-target for in silico modeling

The P450 cytochrome family is one of the most important enzymes that is responsible for the phase I metabolism of about 80% of the drugs [1]. The drug response can be dramatically altered by differences in enzymatic activity (increased, decreased, none) caused by genetic polymorphism. Family member CYP2D6, responsible for around 25% of the drug metabolism, is a highly polymorphic enzyme with over 100 allelic variants identified (http://www.PharmVar.org). Information regarding the potential interactions of CYP2D6 with a drug and its dynamic behavior can help to avoid several drug toxicity/safety issues (i.e. drug inactivation, drug accumulation, or drug-drug interactions (DDIs)) leading to reduced or lost pharmacological efficacy and adverse drug effects. Computational tools that provide such information are therefore desirable to aid in the optimization process of lead compounds in a cost-efficient manner. Here, we will present in depth which in silico tools can be of value for anti-target modeling using CYP2D6, one of our major research topics, as illustrative show case. 

[1] Shu-Feng Zhou, Jun-Ping Liu & Balram Chowbay (2009) Polymorphism of human cytochrome P450 enzymes and its clinical impact, Drug Metabolism Reviews, 41:2, 89-295.