Computer-Aided Design for Synthetic Biology

Abstract

Computer-aided design (CAD) for synthetic biology has been proposed to parallel similar efforts in other engineering disciplines, such as electrical engineering or mechanical engineering. However, there is an important distinction between the fields, which is that the mechanisms by which biological systems function are not currently fully understood in sufficient detail to make completely predictive tools. Computational models of biological systems provide, at best, a qualitative understanding of the system under investigation. Quantitative models are limited by the large number of unknown parameters in any given biological system as well the lack of understanding of the detailed mechanisms. It is difficult to determine how much detail is required for predictable design of biological systems. Even assembling individual DNA sequences has shown to be unpredictable due to secondary DNA structures. As a result, the phrase ‘computer-aided design’ takes a very different meaning in synthetic biology: designing biological systems is as much an exploratory process as it is a rational design process. Through design and experimentation, the science of engineering biology is furthered, and that knowledge must be explicitly fed back into the design process itself. Due to its complexity, the challenge of predictably designing biological systems has become a community effort rather than a competitive effort. Consequently, several software developers in synthetic biology have recognized that supporting a community is a necessary component in synthetic biology design applications. Existing software tools in synthetic biology can be categorized into a three broad categories. First, there are software tools for mathematical analysis of biological systems. This category also includes tools from the field of systems biology. Secondly, there are software tools for assembling DNA sequences and analyzing the structure of the resulting composition. This category builds on concepts from genetic engineering for manipulating DNA sequences. The third category of tools are for database access. Synthetic biologists need a catalog of biological components, or ‘parts’, from which systems can be built; therefore, databases, whether local or distributed, are integral for synthetic biology research. This chapter will cover these categories of tools and how they contribute to synthetic biology. We also consider design by combinatorial optimization, which may work well in biological engineering due to properties of DNA replication.