Automatic Design Tools for Synthetic Biology

We present our molecular modelling and systems biology tools for the de-novo design of proteins and their networks. To computationally design proteins, we have developed automatic design software based exclusively on molecular mechanics. We show some recent experimental validations, such as our new thermostable chorismate mutase enyme with minimal amino acid alphabet, or a thioredoxin protein with additional esterase activity. We have also validated our methodology by redesigning a set of small protein domains, where we have found that their similarity with natural protein families. Our protein design tools (Designer and Protdes) require high-resolution protein structure data and a physical model of protein stability and function. We can use our software to design proteins with targeted molecular recognition, novel protein scaffolds, or enzymes with novel substrates. These tools allow the de-novo design of synthetic signal-transduction devices or other protein networks. To design biological networks, we have developed a software (Genetdes) that uses combinatorial optimisation to obtain a gene network with targeted time-response.