Modeling moving washers that help DNA replicate: Computations yield new insights about how motor proteins split double strands

Knowing the structure of a complex biological system isn’t nearly enough to understand how it works. It helps to know how the system moves.

In that light, Rice University researchers have modelled a key mechanism by which DNAreplicates.

Combining structural experiments and computer simulations, bioscientist Yang Gao, theoretical physicist Peter Wolynes, graduate student Shikai Jin and their colleagues have uncovered details about howhelicases, a family of ringlike motor proteins, wrangle DNA during replication. Their work could reveal new targets for disease-fighting drugs.

The synergy between the experiments and large-scale simulations they describe in the Proceedings of the National Academy of Sciences could become a paradigm for modeling of the mechanisms of many complex biological systems.

“These are dynamic processes that cannot be captured well with experimental methods alone,” said Gao, an assistant professor of biosciences and a CPRIT Scholar in Cancer Research. “But it’s important to show the mechanisms of these helicases, because they’re essential for DNA replication, and also possible drug targets.”

Hexameric helicases have six sides that self-assemble from peptides into a washerlike ring that separates the parental double strands of DNA into daughter single strands. Until now, researchers have been unable to pin down how the helicase steps along as it unzips the double strand.

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