[en] De novo protein design is a growing field in protein chemistry, where artificial proteins are first designed in silico and then validated experimentally. Our group has a long tradition in the design of artificial (β/α)8-barrel proteins, known as Octarellins [1]. This fold, also known as TIM-barrel, is widespread in nature, particularly in enzymes, and represent an interesting target for therapeutic or biological applications. Here we present a novel protocol for the de novo design of TIM-barrels.
Both Rosetta and Modeller modeling softwares were used to create the backbone structure of a TIM-barrel fold and to generate more than 10.000 artificial amino acid sequences. Stability was tested for the more interesting models by running molecular dynamics (MD) simulations, using GROMACS. The best models were chosen for protein production and preliminary biophysical characterization.
The design of artificial proteins and the improvement of bioinformatics tools for protein modeling, structure prediction and MD simulations seem to be essential for a comprehensive knowledge of protein structure in general, as well as for an optimal use of the massive amount of data resulting from the numerous genome sequencing projects.
