Researchers from the University of Georgia utilized the Summit supercomputer to study the molecular mechanism for restoring damaged DNA, specifically the nucleotide excision repair (NER) system. This system plays a crucial role in correcting various DNA damage, ultimately protecting the body from premature aging and cancer.
Scientists developed a computer model of a key component of the NER complex called pre-Rore (PINC), which plays a role in regulating the recovery processes in the later stages of repair. The study revealed that the protein components of the NER can alter their form to carry out different DNA recovery functions.
Leading researcher Ivilo Ivanov, a professor of chemistry at the University of Georgia, highlighted that understanding the NER mechanism will lead to deeper insights into the genetic mutations that underlie serious illnesses. The researchers used NAMD software specifically designed for supercomputers to model these processes. With Summit’s computing power of 200 petaflops, detailed simulations were conducted on a microsecond time scale.
“We observed how various PINC components interacted with each other, forming the dynamic modules of this molecular machine,” said Ivanov. The simulations also indicated that mutations impacting the NER typically occur in the most dynamic regions of the complex.
The NER comprises three distinct stages: damage recognition, severity assessment, and direct repair. The XPC protein is responsible for detecting defects, altering the DNA structure to expose the damaged area, and recruiting other proteins to complete the repair process. Mutations in genes like XPF and XPG have been linked to severe conditions such as pigmented xeroderma and Cockayne syndrome, which are associated with increased susceptibility to skin cancer and accelerated aging, respectively.
Although Summit was decommissioned in 2024, scientists are planning to continue their research using its successor, the Frontier supercomputer, which was recognized as the most powerful in the world in 2022. The next phase of the study will focus on transcription-coupled repair (TC-NER), which targets damage in active genes to prevent disruptions in protein synthesis. These investigations present new avenues for understanding genetic diseases and developing effective treatment strategies.