Automation system of design work on the creation of a living organism
Developed CAD for biologistsAnna Sablina, "Eternal Mind"
The TinkerCell program allows you to create models of networks of molecular biological interactions from cellular "parts" available in databases and observe their dynamics. It should become a powerful tool for synthetic biology.Deepak Chandran and Frank Bergmann from the University of Washington in Seattle have developed a CAD analog for visual modeling of molecular biological processes, which supports a multi-stage hierarchy of biological "parts", each of which has a set of attributes.
The largest families of objects are: enzyme, transcription factor, promoter, protein-coding DNA sequence, terminator, mRNA, fluorescent reporter protein. The processes occurring with these objects are also divided into families: biochemical reaction, binding to the promoter, transcription, translation. Examples of attributes are the sequence of monomers and the rate constant. The program allows you to model, and taking into account the spatial organization of cells, the kinetics of processes such as extracellular and intracellular signal transmission by proteins, including those occurring in a network of protein interactions with numerous positive and negative feedback loops, regulation of gene transcription, a signal from fluorescent reporter proteins and more complex, based on the listed, for example, gene regulatory networks. TinkerCell's flexible framework, object structure for modeling allows it to easily adapt to changes in our knowledge about the composition and interactions of biological molecules. It can even be a change in what attributes a certain type of objects is characterized by. Deterministic (definite) and stochastic (with an element of randomness) simulation models, metabolic control analysis, flow balance analysis, one- and two-dimensional stable equilibrium analysis are available.
The databases used provide a set of possible objects (proteins and DNA sequences) for modeling molecular interactions belonging to a particular organism. There is also data on the specific characteristics of the interaction of objects, for example, the binding sites of the transcription factor with the promoter. In addition to using a database, you can enter your element into the system, for example, a DNA sequence, and observe its effect on its behavior.
The program supports modules, which are relatively closed small networks of protein interactions that interact with other similar networks through interfaces.
The program is written in C++ using the Qt library. It provides an extensive API for programming plugins and scripts in C and Python, which allow, on the one hand, to load biological "parts" from databases, and on the other hand, to implement various methods of analyzing the dynamics and stability of the system. For example, a developer with a database of proteins and nucleotide sequences for Escherichia coli can develop a script to access this database from TinkerCell. The program is free and open source software distributed under a BSD-type license that allows you to distribute modified code under a less free license. The main part of the analysis is carried out by C and C++ libraries and Python modules originating from third parties, TinkerCell is only a visual interface and front-end for them. With the help of modules and add-ons created by developers for TinkerCell, users can create models using a visual or scripting interface. The latter uses the Antimony language developed by the same authors.
With the help of the program, you can simulate the effect of various changes on the behavior of a biological system and then compare the result with experimental data to determine the degree of correctness of our ideas about the functioning of organisms. Also, using the program, you can test various methods of synthetic biology.
The program, documentation and training courses are available at http://www.tinkercell.com .