Researchers develop new method for deriving 3-D protein structures from lab-designed DNA sequences, mutant genes

phys.org | 3/25/2019 | Staff
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Sequencing the first human genome was a herculean effort that took 13 years, hundreds of researchers around the globe and billions of dollars.

But recent advances in technology have transformed genome sequencing into a fairly mundane affair with millions of people having sequenced at least parts of their genomes using DNA collection kits available at drug stores.

Leaps - Scientists - Ability - Analyses - Insights

Although these leaps in scientists' ability to perform genetic analyses have yielded untold insights into human heritage, disease and health, the precise meaning behind DNA sequences—how the order of the "letters" in each DNA strand instruct the body's proteins what to become and what to do—remains unclear.

Now, in a scientific first, scientists in the Blavatnik Institute at Harvard Medical School have shown it is possible to determine the 3-D structures of a gene by assessing the effects of lab-made genetic mutations on protein functions.

Team - Findings - June - Nature - Genetics

The team's findings, published June 17 in Nature Genetics, represent a significant step toward linking sequence data with its function in cells. The tool is freely available at https://github.com/debbiemarkslab/3D_from_DMS_Extended_Data .

The current study will be published in parallel with research from a team led by Jörn Schmiedel and Ben Lehner at the Barcelona Institute of Technology that independently arrived at similar results, employing the concept but using a different technique, thus affirming the utility of the approach.

Approach - Study - Scanning - Use - High-throughput

The computational approach used in the study is known as deep-mutational scanning and involves the use of high-throughput sequencing to synthesize various genetic mutations and then determine the mutations' impact on protein function.

By contrast, previous efforts—including work by researchers in the current study—relied on machine learning to glean such 3-D structures from naturally occurring, rather than lab-made, DNA samples.

Study - Researchers - Interactions - DNA - Sequences

In the current study, researchers identified functional interactions within DNA sequences containing instructions for four different proteins and one RNA. From these, the researchers constructed 3-D structures of the...
(Excerpt) Read more at: phys.org
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