Information theory is a powerful tool for understanding the DNA andRNA patterns that define genetic control systems. My theoretical workis divided into several levels. Level 0 is the study of geneticsequences bound by proteins or other macromolecules, briefly describedbelow. The success of this theory suggested that other aspects ofinformation theory should also apply to molecular biology. Level 1theory introduces the more general concept of the molecular machine,and the concept of a machine capacity equivalent to Shannon's channelcapacity. In Level 2, the Second Law of Thermodynamics is connected tothe capacity theorem. This defines the limits of Maxwell's Demon andmolecular computers. The project also has several interrelatedactivities: developing theory, doing computer analysis, runninggenetic engineering experiments and building nanotechnologies. Inlevel 0 I showed that binding sites on nucleic acids usually containjust about the amount of information needed for molecules to find thesites in the genome. Apparent exceptions to this """"""""working hypothesis""""""""have revealed many new phenomena. The first major anomaly was found atbacteriophage T7 promoters, which conserve twice as much informationas the polymerase requires to locate them. One explanation is that asecond protein binds to the DNA; a second one is that the phage usethe excess to take over the cell. In another case, we discovered thatthe F incD region has a three-fold excess conservation, which impliesthat three proteins bind there. We are investigating these and otheranomalies experimentally. An anomaly in the binding sites for the P1RepA protein led to the hypothesis that the initial step of DNAreplication and RNA transcription is a base flipped out from the DNA.The experimental evidence supports this hypothesis. Two graphicalmethods have been invented to display the structure of binding sites.A sequence logo shows the average patterns in a set of binding sites.The patented sequence walker shows individual binding sites.Displaying many walkers simultaneously has become such a powerful toolfor investigating genetic structure that it can replace consensussequences. Walkers can be used to distinguish mutations frompolymorphisms, and this has clinical applications, especially foranalysis of splice junctions. Molecular information theory givesclear concepts of how molecules use energy. Turning this around tellsus how to build molecular devices. A number of nanotechnologyprojects are in progress, including: a molecular computer (EuropeanPatent 1057118, United States Patent 6,774,222), a method for molecular sequencing (patent pending), and a molecular engine (patentpending).
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