Institute for Protein Design

Proteins Made to Order. Researchers at the IPD Design Proteins from Scratch with Predictable Structures

November 8, 2012   Koga, N., Tasumi-Koga R., et al., Nature. 491(7423), 222-227. (2012)

Proteins are an enormous molecular achievement: chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function. Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task.

Now IPD researchers report that they can do just that. By following a set of rules described in a paper entitled “Principles for designing ideal protein structures“a team from David Baker’s laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations. In a blind test, the team showed that the synthesized proteins closely match the predicted structures.

Design of Ideal Folded Proteins

This figure shows the Rosetta@home calculated (high energy red and low energy green dots) for two novel protein designs (Fold- I and Fold-II). Their calculated structures match nicely the experimentally determined structures by NMR.

One might wonder how designing a new protein from scratch could be better than starting with natural proteins, given the head start that nature has in evolving effective functions and stable conformations. In fact, evolution has honed the structures of many proteins so precisely that it can be difficult to get the backbone to budge into another conformation to accommodate a new function, Baker says. “This paper provides the opportunity to design the structure and function at the same time,” says Baker. “Rather than taking an already existing scaffold, now you can design a backbone to order for exactly the function you want to carry out.” That will be the next step — incorporating function into the designs.

Read the full article here.