An emerging field of protein science with the goal of designing proteins to carry out specific functions.

With twenty different sidechains, arranged in an almost limitless number of permutations along a polypeptide chain, the physical and chemical properties of proteins are very malleable. Using these modular molecules, nature has developed systems that convert and store energy, process information, provide structure, and do practically everything required to keep an organism functioning. Spending the last hundred years marvelling at what nature has done with these molecules, scientists now hope to start doing some protein design of their own. Why design a protein to do something when we have established techniques of organic chemistry and materials engineering? Proteins have several advantages:

  • producing proteins is nontoxic - A gene for a designed protein can be inserted into bacteria or some other host and grown in large quantities. The bacteria think the gene is part of their own DNA and happily make the protein. Minimal industrial waste and few noxious chemicals are released into the environment.
  • proteins are very specfic - enzymes have amazingly specifc chemistry and will often only react with a single substrate. Any change in stereochemistry or composition could make a substrate unrecognizable by the enzyme. As a result, the products the enzyme produces are also often highly specific, improving product yields over synthetic methods where one has to purify two very similar chemicals.
  • automated combinatorial screening - Because nature already has automatic processes for producing and modifying proteins, techninques such as directed evolution can generate proteins that adapt to extreme industrial conditions.
Directed evolution is one way of engineering proteins, akin to making innumerable trial-and-error iterations until you find something that works. Another way of approaching the protein engineering problem is de novo design.

De novo design attempts to use our knowledge of the physical and chemical nature of protein folding and protein activity to design proteins of desired function. The current challenge in this field is to design proteins from scratch that adopt a particular structure. Once proteins of the desired shape can be made, the next goal will be to engineer active sites into these scaffolds that bind specific substrates and carry out desired chemistry. The fields of protein folding and protein engineering are feeding into each other. As more is understood about natural proteins, bolder initiatives on the engineering front can be attempted. Conversely, engineered proteins provide highly controlled systems for testing basic rules of protein stability and sidechain interactions.

Protein engineering is a rapidly growing field and much fundamental work still remains to be done. The current goals include building proteins that can remedy disease or clean up the environment. Eventually, protein engineering may be a way of building complex molecular machines that are biologically generated.

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