Effect of mutations on Cytochrome P450 function
Start Date
April 2025
Location
3rd floor - Library
Abstract
The Cytochrome P450 enzymes are a family of enzymes whose primary function is to metabolize drugs and toxins. These enzymes use a heme cofactor to carry out their function. Several mutations in CYP proteins are known to occur. A recent paper by Zhou and Lauschke (The Pharmacogenomics Journal, 2022, 22:284-293) described the genetic distribution of these mutations along with their effects on drug metabolism. The goal of our project was to model mutations in Cytochrome P450 (CYP) enzymes to understand how the mutations affect drug metabolism by these enzymes. We modelled several mutations in 3 CYP proteins using computer-based tools, such as SwissDock and Foldit. SwissDock allows us to explore how the mutations would affect drug binding to the enzyme. Foldit helps us understand how the mutations affect the stability of the CYP itself. We compared our modelling results for each mutation in each CYP with the known metabolic effect of each mutation as described by Zhou and Lauschke. We expect that mutations leading to increased drug metabolism will show tighter binding of a drug in the results from SwissDock. Slower drug metabolism should correspond to weaker binding as shown by SwissDock. Our future goals therefore are to examine more mutations in more CYP proteins to understand how they affect drug metabolism.
Effect of mutations on Cytochrome P450 function
3rd floor - Library
The Cytochrome P450 enzymes are a family of enzymes whose primary function is to metabolize drugs and toxins. These enzymes use a heme cofactor to carry out their function. Several mutations in CYP proteins are known to occur. A recent paper by Zhou and Lauschke (The Pharmacogenomics Journal, 2022, 22:284-293) described the genetic distribution of these mutations along with their effects on drug metabolism. The goal of our project was to model mutations in Cytochrome P450 (CYP) enzymes to understand how the mutations affect drug metabolism by these enzymes. We modelled several mutations in 3 CYP proteins using computer-based tools, such as SwissDock and Foldit. SwissDock allows us to explore how the mutations would affect drug binding to the enzyme. Foldit helps us understand how the mutations affect the stability of the CYP itself. We compared our modelling results for each mutation in each CYP with the known metabolic effect of each mutation as described by Zhou and Lauschke. We expect that mutations leading to increased drug metabolism will show tighter binding of a drug in the results from SwissDock. Slower drug metabolism should correspond to weaker binding as shown by SwissDock. Our future goals therefore are to examine more mutations in more CYP proteins to understand how they affect drug metabolism.
