ATLANTA—Ivaylo Ivanov, associate professor of chemistry at Georgia State University, will be among the first scientists to perform research using Summit, the world’s most powerful scientific supercomputer, at the Oak Ridge National Laboratory (ORNL) in Tennessee.
Summit is eight times more powerful than ORNL’s previous top-ranked system, Titan, enabling scientific inquiries that were previously impractical or impossible.
Ivanov was among the first to test the machine in spring 2018. Summit goes into full production in January 2019, which is also when Ivanov’s yearlong project will begin.
Ivanov will be studying human transcription, the process by which genetic information in a strand of DNA is copied into RNA. RNA serves as the delivery system for the instructions encoded in the DNA. These instructions are used to arrange and connect the amino acids that make up proteins, which are responsible for most of the body’s major functions.
In the process of transcription, a molecular machine travels along the DNA, opening up the bases to unravel the double helix into two single strands and transcribing the information only from one of those strands — the template strand — before closing up the two strands again.
This machine is known as human RNA Polymerase II, and Ivanov is studying how it functions using large-scale molecular simulations. Improving understanding of the transcription process could allow scientists to learn more about the origins of diseases, including cancer, diseases of aging or neurological conditions.
“In recent years, it has become possible to collect structural snapshots of the transcription initiation machinery through cryo-electron microscopy,” says Ivanov. “The question is how to connect those and produce a comprehensive view of the function of this complex molecular machinery. That’s where computation can play an important role.”
In the simulations, Ivanov will use the supercomputer to continuously track millions of atoms at every stage of the molecular process.
“What we’re putting into the computer is what we’ve learned from cryo-electron microscopy about the various functional states of RNA Polymerase II,” he says. “We’re trying to link those states and uncover how the transcription machinery transforms as it carries out its biological function.”
Ivanov’s work focuses on computational biology and biophysics, molecular modeling and simulations, drug design, computational chemistry, biological assemblies and mechanisms of genome duplication and maintenance.