Molecular computer circuit diagram for a NOR gate made
from one repressor protein blocking two different activator
proteins. Fis Flip Flop - two adjacent Fis protein binding sites
compete for Fis protein binding Molecular Computing Elements:
Gates and Flip-Flops

TD Schneider, PN Hengen (NCI)

Description of the Invention:
The basic idea of creating a molecular logic NOR gate is shown in the figure at the top left. An RNA polymerase (cyan) can be activated (arrows) by DNA binding protein A (green) which binds site a (purple). Two other proteins R1 and R2 bind the DNA at sites r1 and r2 that overlap with site a and interfere with binding of A. The resulting logic is a NOR gate. All Boolean circuits can be built from NOR gates so it is possible to build entire molecular computers with this gate.

The nice thing about such a logic gate is that is it very compact.

A more advanced form would use DNA binding proteins that stick strongly but which can be kicked off the DNA by GTP hydrolysis. I do not know if such things exist in nature, but it is likely that one could evolve them in the lab. The GTPase DNA binder can be triggered to come off the DNA by a GAP protein which could also bind DNA nearby. It is possible that such structures sitting on a meshwork of DNA origami could do lots of complex logic. Of course it would not be as fast as electronics but it could be grown and be massivly parallel (eventually).

Informal Description of the Invention:
A completely molecular computer can be constructed using designed DNA and DNA binding proteins. Several versions of the device are possible. In the simplest device, bacteria or other cells are programmed with DNA sequences and DNA binding proteins that execute logical Boolean operations. It is also possible to construct molecular computers outside cells, but in this case special attention must be paid to providing energy to run the computer. The technology is based on the concept of a molecular flip-flop in which one or more proteins compete for binding to binding sites that overlap. Because only one protein can bind at a time but there are two ways for it to bind, the method can also be used to double the sensitivity of diagnostic assays.

Formal Description of the Invention:
The present invention is a method and apparatus for molecular computing which provides for molecular logic devices analogous to those of electronic computers, such as flip-flops, AND gates, etc. Coupling of the gates allows for molecular computing. The method allows data storage, the transformation of binary information and signal readout. Possible applications include encoding ``read only'' memory for microscopic identifiers, digital control of gene expression, and quantification of analytes. The computing elements also provide means for complex regulation of gene expression.

European Patent No: 1057118 (PDF)
Granted 2003 May 28.

United States Patent 6,774,222
Granted August 10, 2004

United States Patent 6,774,222 at the US patent office
United States Patent 6,774,222 at

Fis Flip Flop - two adjacent Fis protein binding sites
compete for Fis protein bindingMolecular Flip-Flops Formed by Overlapping Fis Sites is a paper describing the biology behind the idea.

A cartoon.  A fellow enters a lab where a woman is sitting at a table with a graduated cylinder, an Erlenmeyer flask and she is holding a round bottom flask.  He says 'I've done it!!' I've created the world's first fully-operational molecular computer ..!!' She is puzzled and then says 'Amazing!!  How did you account for quantum interference effects..?' He says 'I incorpporated them into the design rather than trying to eliminate them!' She responds 'But how did you link up all those tiny circuits?' 'No problem-I modified a few enzyme-linking tricks borrowed from the molecular biologists!' 'And can it do real calculations?' 'Can it!?  So far it's come up with 15 alternate proofs for Fermat's last theorem ..!!' 'Speed?' 'I'm estimating it runs at several trillion computations per second'.  They both stop and smile.  He then says 'In fact, at the moment I'm only having one small problem with my molecular computer...' 'Which is..?' He is holds a magnifying glass and says 'I can't find it again...'
From (the cartoon may have been removed). Reproduced with permission since this is a research/educational site.

Federal Register: May 15, 1998 (Volume 63, Number 94) Page 27095-27097
Federal Register announcement vol 63, no. 94, page 27095, Friday, May 16, 1998, in pdf format

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Schneider Lab

origin: 1998 June 16
updated: 2022 Jan 18: improve description
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