An interchangeable receptor for the detection of compounds in soil and air is essential for our system. By using a modular system, the receptor can be changed easily to create a adaptable plant for detection of chemicals. This allows us to adapt our system for further chemical weapon degradation products, but also it’s adaption according to the needs for further applications. This can be achieved by computational protein design.
We created a adaptable protein design pipeline which enables the reliable design of receptors for a chemical of interest. We decided to use Rosetta as a versatile and powerful tool to simulate docking and to design improved structures. Rosetta is popular, well maintained and open-source tool for protein structure prediction. Its range of functions was expanded from structure prediction to many different areas. The predictions are based on the energy profile of the structures.
To understand the procedure, it is important to note that protein design and most of its associated tasks such as structure prediction are very complex assignments from the computational perspective. Therefore it is not guaranteed the the algorithim produces the optimal structures. However, many algorithms include heuristic steps that often produce good results. To increase the probability to receive good results, most of the runs are repeated several times and the best results are selected.
An advantage of Rosetta is the possibikity of usage usage through many different frameworks. We used “RosettaScripts”, an XML-based format that allows for flexible tool usage as well as the compatibility with EvoDock, a script that adds an evolutionary approach to speed up the design process.
Our receptor engineering approach can be split into the following procedures:
- Design (EvoDock)
- Test Structure
The individual steps will be described in the following.