[tt] physorg: more on DNA reaction design helper

[Alejandro Dubrovsky]

(
http://www.physorg.com/news119804760.html
)

Programming Biomolecular Self-Assembly Pathways
Nature knows how to make proteins and nucleic acids (DNA and RNA) dance
to assemble and sustain life. Inspired by this proof of principle,
researchers at the California Institute of Technology have demonstrated
that it is possible to program the pathways by which DNA strands
self-assemble and disassemble, and hence to control the dynamic function
of the molecules as they traverse these pathways.

The team invented a versatile DNA motif with three modular domains that
can be made to interact with complementary domains in other species of
the same motif. Rewiring these relationships changes the dynamic
function of the system. To make it easier to design such systems, the
researchers developed a graphical abstraction of the motif that can be
used to write "molecular programs."

As described in the January 17 issue of the journal Nature, the team
experimentally demonstrated the execution of four such programs, each
illustrating a different class of dynamic function.

The study was performed by a team of four at Caltech: Niles Pierce,
associate professor of applied and computational mathematics and
bioengineering; Peng Yin, senior postdoctoral scholar in bioengineering
and computer science; Harry Choi, graduate student in bioengineering;
and Colby Calvert, research technician.

Programming pathways is a bit like planning a road trip. The final
destination might be important, but the true enjoyment is picking and
traveling the route. In the test tube, the goal is not solely to direct
the molecules to assemble into a target structure, but to engage them in
a sequence of maneuvers so as to implement a prescribed dynamic function
before the system reaches equilibrium. The energy to power the reactions
is stored in the molecules themselves. Each molecule is initially
trapped in a high-energy state so that it can release this energy as it
engages in handshakes with other molecules.

A molecular program is written and executed in four steps. First, the
intended assembly and disassembly pathways are described using a
graphical abstraction called a "reaction graph." This molecular program
is then translated into molecular mechanisms described at the level of
base pairing between individual complementary bases. Computational
design algorithms developed in the group are then used to encode this
mechanism into the DNA sequences. Finally, the program is executed by
mixing the physical molecules.

To demonstrate this approach, the team experimentally demonstrated a
variety of dynamic functions: catalytic formation of branched junctions,
cross-catalytic circuitry with exponential system kinetics, triggered
dendritic growth of molecular "trees," and autonomous locomotion of a
molecular bipedal walker.

As Pierce describes it, these results take them closer to achieving a
long-term goal of creating a "compiler for biomolecular function"--an
automated design tool that takes as input a molecular program and
provides as output a set of biomolecules that execute the desired
function. He remarks, "It's about time for the stone age of molecular
compilers to begin."

Source: Caltech