Biomedical Engineering Reference
In-Depth Information
Figure 9. Operation of the biomolecular automa-
ton if all three RNA molecules are present
•
The
restriction enzyme
is a protein with
two ends that asymmetrically cut the two
strands of the hairpin to assure that it always
exposes a toehold.
•
The
transition molecule
consists of a double
RNA strand also with an exposed toehold. Its
goal is to make the automaton move from one
state to the next depending on whether or not
disease-associated RNA is present. There are
four types of transition molecules:
yes-yes
,
yes-no
,
no-no
and
release
. For example, a
yes-no
transition molecule recognizes a
yes
state and makes the restriction enzyme cut
the necessary hairpin strands to make the
next state
no
. The four transition molecules
differ as to their length and the toehold they
expose.
°
The length has the function of making
the enzyme ends the right size to cut the
hairpin so that the toehold it exposes
represents the next state.
°
The toehold has the function of recog-
nizing the current state of the automaton
from the hairpin toehold and binding to
this toehold. The toehold of a transition
molecule can be:
yes 1'
,
yes 2'
,
yes 3'
,
yes release'
and
no'
. These toeholds are
complementary to the possible hairpin
toeholds:
yes1
,
yes 2
,
yes 3
,
yes release
and
no
respectively. There is no transi-
tion molecule with a
no release'
toehold
that is complementary to the hairpin's
no release
toehold. This assures that
no enzyme can cut the hairpin in this
case and the drug is not released.
•
yes 1
,
yes 2
,
yes 3
and
yes release
that rep-
resent the state
yes
.
•
no
and
no release
that represent the state
no
.
At the end of the computation, the hairpin can
only expose one of the following toeholds:
yes
release
or
no release
. If it exposes
yes release
,
the computation ended with the
yes
state and
the drug is released. If it exposes
no release
, the
computation ended with the
no
state and the drug
is not released.
During the computation process, the automa-
ton moves from one state to another through a
complex
formed by a restriction enzyme linked
to a transition molecule.
In the following we explain how this biomo-
lecular automaton works. In Figure 9 the hairpin's
original state is
yes
, represented by the exposed
toehold
yes 1
. If RNA 1 is present, a cutting
enzyme linked to a
yes-yes
transition molecule
with the
yes 1'
toehold appears due to different
competitive hybridization processes, which, for
simplicity's sake, we will not discuss at length
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