TangleSolve



    Download one of two free versions  Applet Version and Application Version.

The Applet Version runs directly off the web-browser and may be slower depending on the internet connection.  The Application Version can be downloaded to the users hard drive and can be executed locally.  Specific directions for Windows and Unix can be located at How to Download Application Version

TangleSolve is a web-band Java applet that runs in every environment.  Most systems run full versions of Java.  If not, the user may need to download Java Plug-in to run the Applet Version.  Or Java Run-time to run the application version.


Background Information 


Figure 1. Site-specific recombinases fill the role of molecular scissors because they are able to cleave double-stranded DNA. In a single enzymatic event the enzyme recognizes specific recombination sites, mediate a double-stranded break at the core regions of each of the sites, recombines the lose ends, and reseals the recombined strands as illustrated above.

TanlgeSolve is a Java computer program used in the analysis of site-specific recombination.  Site-specific recombination is mediated by the protein site-specific recombinase and is important because of its key role in a wide variety of biological processes such as: deoxyribose nucleic acid (DNA) rearrangement, integration and excursion of viral DNA into and out of a host genome, and resolution of multimeric DNA molecules to allow proper segregation at cell division i.e. Tn3 resolvase (reviewed in Ernst and Sumners (1990)) and Xer C and Xer D recombinases (reviewed in Vazquez et al (2004)). Site-specific recombinases fill the role of molecular scissors (Figure 1) and are able to change the topology of DNA by introducing double-stranded breaks at two specific DNA sites, recombine the ends of the specific sites, and past the recombined sites' ends together. This process can be considered to occur in two stages: synapsis and strand exchange. Synapsis, the first stage of recombination, is when the recombination sites and accessory proteins on the same or different DNA substrate molecules are brought together globally prior to recombination to form a specific synaptic complex. The bounded substrate and enzyme are also known as the pre-recombinant-DNA complex (reviewed in Buck and Flapan (2007)). The second stage, strand-exchange, can be thought of as the recombination sites locally being cleaved and exchanged. This is known as the post-recombinant complex (reviewed in Zheng et al (2000) and Vazquez et al (2004)). The post-recombinant DNA molecule unbounded by the enzyme is known as the DNA product.

If the enzymes action is known (or believed) to act non-processively or
processively, then TangleSolve will compute the solutions to the systems respectively. TangleSolve is an interactive application which implements the Tangle Method and offers an easy-to-use graphical interface for analyzing and visualizing topological mechanisms of recombination. The Tangle Method converts the biological problem of solving the enzymatic action into the mathematical problem of computing the geometrical and topological configuration of the DNA molecule before, during, and after the recombination event.  This is done by translating a recombination event into a system of tangle equations.  A tangle is a 3-dimensional ball with two non-self-intersecting arcs.  The Tangle Method finds solutions to tangle equations which are rational or sums of rational tangles, i.e. which can be easily wound and unwound by smooth deformations. The following example illustrates a tangle equation and its graphical representation within TangleSolve:


N((0) + (2,2,2) + (0))            = 632*            = < 1,1,2,1,1 >

Figure 2. Standard knot diagram for 632* from D.Rolfsen's Knots and Links

This program is concerned with site-specific recombinases that converts unknotted circular DNA substrates into knotted or linked DNA of specific topology.  TangleSolve assumes that substrates and products of recombination are 4-plats because most knots and links seen in biology are 4-plat (or 2-bridge knots and links).

Given a link of specific substrate and product topologies, TangleSolve finds all rational and sums of rational tangle solutions to the corresponding system(s) of tangle equations.  The solutions are displayed as knot and tangle diagrams as shown in Figure 3.


For a descriptive overview of the mathematics and biology involved see Background
For an informative tutorial on how to use TangleSolve see Tutorial

    Figure 3. Example of TangleSolve solution. Pictorally from left to right: numerator addtion, knot or link illustration by D.Rolfsen, 4-plat.



For questions please contact: mariel@math.sfsu.edu