How to design proteins ?

Don’t let the simplicity of this question fool you! Indeed, protein design hides multiple fundamental questions - which essentially shows how little we know about these very well-known molecules.

Roughly speaking, two approaches are fighting: i) machine learning takes natural protein examples to design new ones, and ii) physics explicitly models the details hidden in protein atoms! I followed the second option, where in collaboration with experimentalists, we not only designed proteins for molecular structure stability but also new catalytic proteins (enzymes). The methods we worked on are implemented in the Proteus Software developed in Thomas Simonson’s lab.