During DNA repair process, Uracil-DNA glycosylase (UDG) is one of the most essential enzymes that participate base excision repair (BER) mechanism, the function of UDG is to repair the uracil-induced DNA lesion by removing a particular base called uracil from damaged DNAs. Uracil in DNA may occur due to the cytosine deamination or deoxy uridine monophosphate (dUMP) residues misincorporation during DNA synthesis. Medical evidences haven shown that an abnormal expression of UDG is related to different types of cancer, including colorectal cancer, lung cancer, liver cancer, etc. Therefore, the research of UDG is important in cancer treatment and prevention, as well as other clinical activities. In this project, we applied multiple computational methods to study the UDG in several perspectives: Understand the stability of UDG enzyme in different pH conditions; study the differences in charge distribution between the pocket side and non-pocket side of UDG; analyze the field line distribution at the interfacial area between UDG and DNA; perform electrostatic binding forces analyses of special region of UDG (pocket area) and target DNA base (uracil); as well as investigate the charged residues on UDG binding pocket and binding interface. The results indicate that it is the whole UDG binding interface rather than the UDG binding pocket area alone who provides the binding attractive force to a damaged DNA at uracil base. This finding provide essential evidences to explain the processes of how UDG and DNA interact with each other, which will contribute to the cancer treatment and prevention area in the future.

Computational study on the uracil-DNA glycosylase (UDG) in DNA repair

ACS Spring 2022

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