Brave New World of Protein Design

[BillTre]

Here is an NY Times article by Carl Zimmer, describing recent advances in predicting protein design.
This involves going from an amino acid sequence to a predict a protein 3D structure or going from what you want in a protein to the amino acid sequence that can generate it.

This has long been a big computational problem.
They seem to have it solved (so claims the article).
If so, this extends our ability to understand and control the stuff biology is made of and to intentionally modify it to our will. This will close the gap between genetic programming and biological organisms vested with the particular desired traits.

Proteins are a step beyond the rather direct computer-like information conveying mechanisms that nucleic acids (RNA and DNA) use to store and utilize information.
That information, stored by natural selection over millions of years, is utilized when proteins are created (using the encoded mechanisms of ribosomes and tRNAs). Proteins can have a wide variety of shapes, chemistries, binding sites, different stable conformations, etc.
Proteins can have direct effects on cellular properties and behavior: receptors (binding and responses), cytoskeleton (cell motility, strength/resistance of cell to mechanical distortion), production of signal molecules, ...

The relationship in biology amino acid sequence and protein structure is like the relationship between letters and words in our written language. Going from a moderately sized set of components (26 letters; 20+ amino acids) to an almost vast number of possible words or proteins.

 

[Greg Bernhardt]

This has long been a big computational problem.

Quantum computing could help?

 

[BillTre]

I believe this has been suggested as a good problem for quantum computing.

 

[r8chard]

Consistent improvement of the tools for research. Along with consistent filtering of data for accuracy. Means improving the quality of conclusive, verifiable data.

And then? We get to start all over again, striving for the next goal.

 

[Ygggdrasil]

David Baker, the scientist profiled in the NY Times piece, has definitely made some big strides in the field (almost all of the major breakthroughs in the area of protein design have come from his lab). Back in 2003, his lab was one of the first to report designing a protein structure from scratch, synthesizing the gene, producing the protein, and showing that it folded into the shape they wanted (http://science.sciencemag.org/content/302/5649/1364.long). This protein, however, was very simple and did not perform any function. Over the past decade and a half, his lab has succeeded in designing functional proteins and improving the complexity of the structures they are able to design. As discussed in the article, his lab has recently published about designing new enzymes to bind and detect various chemicals as well as to bind proteins in flu to perhaps act as an antiviral agent. More impressively, his lab has made the first step towards creating artificial viruses by creating a protein shell that can bind and encapsulate an RNA genome (https://www.nature.com/articles/nature25157). These artificial viruses could act as new tools for gene therapy, aiding in delivering genes to diseased cells inside of the body, though one could conceive of more nefarious purposes for artificial viruses as well.

There are still unsolved problems in the field of protein design, however. For example, in 2008, his lab reported computationally designing enzymes to catalyze new reactions (http://science.sciencemag.org/content/319/5868/1387.long and https://www.nature.com/articles/nature06879), though these enzymes catalyze very simple reactions (that already occur to some extent without the enzyme present) and the designed enzymes are not as efficient as natural enzymes. Thus, there is a lot more to learn about how to make custom designed enzymes for arbitrary chemical reactions.