| dc.description.abstract | The Epstein-Barr virus (EBV) and Kaposi’s Sarcoma-associated herpesvirus (KSHV) are prevalent worldwide with a 95% infection rate for EBV and as high as 50% for KSHV in adults. These herpesviruses code for DNA Origin-Binding Proteins (OBPs) such as Epstein-Barr Nuclear Antigen 1 (EBNA1) in EBV and Latency-Associated Nuclear Antigen (LANA) in KSHV. Both of these OBPs are responsible for oncogenic conditions (Hodgkin’s lymphoma, Kaposi’s Sarcoma, and gastric cancers) and episome maintenance during latency phases, making them attractive targets for inhibitor therapy. This study focused on understanding the atomic interactions between EBNA1, LANA, and their corresponding viral DNAs (vDNA) using molecular dynamics simulations of the EBNA1-vDNA(EBV) and LANA-vDNA(KSHV) complexes. Our analysis focused on calculating relative binding free energies (RBFE) allowing for a comparison to be made between EBNA1 and LANA RBFE. We found that EBNA1 binds more strongly to vDNA when compared to LANA. We determined noncovalent interactions, root-mean-squared fluctuation, root-mean-squared deviation from the initial structure, solvent-accessible surface area, and calculated entropy using the maximum information spanning tree method to further characterize the bound versus free states of these proteins. We found EBNA1 to make more bonds with vDNA, have a larger binding area, and the RBFE to be -224.56 ± 33.1 kcal/mol for EBNA1 compared to -105.16 ± 17.9 kcal/mol for LANA. Determining the RBFE and characterizing the atomic interactions from simulating these viral proteins may contribute to inhibitor development for KSHV and EBV. | |
