Understand the mechanisms of Uracil-DNA glycosylase using computational methods
Disciplines
Computer Sciences | Health Information Technology
Abstract (300 words maximum)
DNA mutations can happen as many as 1x10^5 to 1x10^8 times a day. Uncorrected DNA damage causes genetic alterations with unknown consequences. These mutations are commonly the cause of lung cancer, but UDG is a protein that can fix this damage. Understanding how this process occurs and how the body repairs the damage is an important part in furthering cellular science. This project is designed to study this process, more specifically focusing on the BER method of DNA repair by examining Uracil-DNA glycosylase, also known as UDG, with AP: A and AP: G containing DNA. We utilized ChimeraX to visualize the electrostatic surface of both versions of UDG (PDB ID: 2DDG and 2DEM). We found that these two models form different surfaces, indicating that the binding processes and interaction mechanisms with DNA are different. DNA is overly negatively charged while only the pocket of UDG is positively charged. The back of UDG is negatively charged and the sides have mixed charges to repel the DNA. The advantage of this distribution is that the DNA and UDG pocket are more likely to bond accurately. From our observation 2DDG is more positively charged in the pocket area. There is also a slight shape difference between the two UDG models. This can be attributed to the different amino acids in the model which can affect the bonds between the molecules in each model. The process is not fully understood but these charges aid the removal of uracil. This work brings insight for DNA researchers to understand the differences in binding mechanisms. This project will continue researching DNA-Protein interactions to gain useful insight for DNA researchers about the difference in binding mechanisms.
Academic department under which the project should be listed
CCSE - Information Technology
Primary Investigator (PI) Name
Chloe Yixin Xie
Understand the mechanisms of Uracil-DNA glycosylase using computational methods
DNA mutations can happen as many as 1x10^5 to 1x10^8 times a day. Uncorrected DNA damage causes genetic alterations with unknown consequences. These mutations are commonly the cause of lung cancer, but UDG is a protein that can fix this damage. Understanding how this process occurs and how the body repairs the damage is an important part in furthering cellular science. This project is designed to study this process, more specifically focusing on the BER method of DNA repair by examining Uracil-DNA glycosylase, also known as UDG, with AP: A and AP: G containing DNA. We utilized ChimeraX to visualize the electrostatic surface of both versions of UDG (PDB ID: 2DDG and 2DEM). We found that these two models form different surfaces, indicating that the binding processes and interaction mechanisms with DNA are different. DNA is overly negatively charged while only the pocket of UDG is positively charged. The back of UDG is negatively charged and the sides have mixed charges to repel the DNA. The advantage of this distribution is that the DNA and UDG pocket are more likely to bond accurately. From our observation 2DDG is more positively charged in the pocket area. There is also a slight shape difference between the two UDG models. This can be attributed to the different amino acids in the model which can affect the bonds between the molecules in each model. The process is not fully understood but these charges aid the removal of uracil. This work brings insight for DNA researchers to understand the differences in binding mechanisms. This project will continue researching DNA-Protein interactions to gain useful insight for DNA researchers about the difference in binding mechanisms.