Using Summit’s 200 petaflops of number-crunching fury, researchers modelled the pre-incision complex (PInC), a critical cog in the nucleotide excision repair (NER) machinery. They uncovered how it functions at an atomic level.
Led by Georgia State University’s Ivaylo Ivanov, the boffins ran molecular dynamics simulations using the Nanoscale Molecular Dynamics (NAMD) software to see how the PInC components move in synchronised chaos.
The study, published in Nature Communications, revealed how this DNA-repairing contraption subdivides into dynamic communities—essentially the moving parts of a microscopic molecular machine.
Ivanov said that computationally, once you assemble the PInC, molecular dynamics simulations of the complex become relatively straightforward, especially on large supercomputers like Summit.
Nanoscale Molecular Dynamics, or NAMD, is a molecular dynamics code designed explicitly for supercomputers and is used to simulate the movements and interactions of large biomolecular systems that contain millions of atoms. Using NAMD, the research team ran extensive simulations.
The number-crunching power of the 200-petaflop Summit supercomputer -- capable of performing 200,000 trillion calculations per second -- was essential in unravelling the functional dynamics of the PInC complex on a timescale of microseconds.
"The simulations showed us a lot about the complex nature of the PInC machinery. It showed us how these different components move together as modules and the subdivision of this complex into dynamic communities, which form the moving parts of this machine," Ivanov said.
This is more than just a flashy computer simulation. The findings have real-world implications, particularly for those suffering from conditions linked to faulty NER machinery.
Mutations in the XPF and XPG genes are known to cause nasty disorders like xeroderma pigmentosum, which makes sufferers highly susceptible to skin cancer, and Cockayne syndrome, which accelerates ageing and impairs growth. By pinpointing the most dynamic regions of the PInC complex—often where these damaging mutations occur—scientists can better understand how these conditions develop and potentially how to tackle them.
