Cracking the HIV Code

Bruce Johnson, Advanced Science Research Center, has NIH grants to help fight HIV.Viruses like HIV and Zika pose grave risks to global public health. HIV remains one of the world’s top killers despite the powerful antiretroviral drugs used to treat it. Zika, so far, has eluded a vaccine. But software being developed by Bruce Johnson, senior research director of computational sciences in the Structural Biology Initiative at the Advanced Science Research Center at the Graduate Center, CUNY, holds the promise of new treatments.

This year alone, Johnson has received three grants from the National Institutes of Health — a coup in today’s funding environment — to hone the software he developed to help researchers understand the structures of the proteins and nucleic acids that make up viruses such as HIV and Zika.

HIV is a specific focus of one of the grants. Johnson is one of about 20 researchers working on the grant from across the country and even as far as Scotland working to understand the structure of the HIV RNA molecule in order, ultimately, to develop new HIV drugs, ideally ones that are more effective and more affordable. 

Today’s HIV drugs attack the proteins in the virus, making it easier for the virus to develop resistance, especially when doses are missed.

The team is using nuclear magnetic resonance (NMR) spectroscopy, among other techniques, to create a three-dimensional picture of RNA. Johnson likens NMR spectroscopy to the magnetic resonance imaging (MRI) scanners that have become prevalent in health care.

The big difference is that MRI relies on a straightforward set of calculations to create an image. Generating a three-dimensional model of a molecule, by contrast, involves collecting and analyzing, via computer, reams of data about the location of different types of atoms within the molecule.
“Everything in science these days pretty much relies on some sort of computational analysis,” Johnson said.

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That’s where Johnson’s software, NMRViewJ, comes in. He developed it early in his 15-year tenure at Merck, where he used NMR spectroscopy to help with drug discovery. “There was a period of new experiments, new ways of doing things in the NMR field, and there just wasn’t software to take advantage of the new experimental data,” he said.

In 2005, he started his own company, One Moon Scientific, to commercialize the software, which is now a leader in the field. So far, researchers have cited NMRViewJ in over 2,500 papers. “I’m sure there are many people that use it and never bother to cite it,” Johnson added with a chuckle.

The software figures prominently in Johnson’s two other NIH grants. He is a co-principal investigator on a five-year grant to develop a national center for measuring the motions of the proteins in RNA molecules.

The project has broad implications for drug development. “If you’re trying to design a drug to target the RNA molecule of HIV and it’s very rapidly moving, you can’t just think about one static structure,” Johnson said. “You really have to think about the motions of these molecules in order to think about how you would design or discover drugs to target them.”

The third grant — $1.25 million — goes directly to Johnson for developing an integrated software package for NMR analysis. Currently, researchers use different software for the various steps in analyzing NMR spectroscopy data, making the science cumbersome. Having a suite of software for the entire process would make NMR spectroscopy more user-friendly and, ultimately, more widespread.

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Johnson, who was trained as a zoologist, is a believer in interdisciplinary approaches to science. That is one reason he especially enjoys working at the ASRC. With five different research initiatives in one building, the potential for collaboration across disciplines is vast.

At present, though, he is concentrating on his grants, particularly on building a team of computational scientists to assist him. “I’m most excited about building up a group of people to work on these,” he said. “When we have new ideas for coding, we’ll have the resources to push forward.”

Submitted on: NOV 10, 2017

Category: General GC News | Grants