Imagine synthesizing entire organisms on a computer, developing proteins that can destroy tumors, and even engineering structures to detect in vivo changes in body chemistry. Last Friday, Dartmouth assistant professor Gevorg Grigoryan described his use of bioinformatics to alter the paradigm of bionanotechnology.

 

Grigoryan researches proteins, which he calls “nature’s universal tools.” Indeed, proteins are essential to a wide range of cellular processes, including the breakdown of glucose, cytoskeletal transport, and the regulation of gene expression. Amazingly, nearly all the diversity in this proteome stems from a simple subunit code of 20 amino acids. So the question Grigoryan asked was, “could you program this code?”

 

He decided to exploit the fact that proteins are made up of amino acids, which assume functional conformations in polymeric form. Grigoryan designed a computer program using information from the Research Collaboratory for Structural Bioinformatics Protein Database that, with just an amino acid sequence, can be used visualize what a protein would look like geometrically, as well as predict its biochemical significance.

 

Grigoryan tested his computer code on a family of transcription factors involved in gene activation called basic leucine zipper domains (bZIPs). Using his program, Grigoryan was able to predict how bZIPs would interact with each other and form complexes simply by looking for similar structural motifs. Next, he used his program to predict how a synthetic protein would act.

 

Single–walled carbon nanotubes (SWNTs) are nano–cylinders made of carbon molecule–based graphene sheets that are rolled together to form tubes. Many labs have marveled at the fascinating properties of SWNTs, but the problem is they are not biologically functional or programmable.

 

Grigoryan wanted to synthesize a protein that could wrap around and thereby interact with the SWNTs to make them programmable. Pursuing this idea, his lab was able to develop a helical protein rich in small, hydrophobic amino acids like glycine that paralleled the periodicity of the SWNTs surface, thus creating proteins that wrapped around the SWNTs.

 

One application of such a protein coil is conjugating the chemical functional groups of the amino acids to gold nanoparticles for therapeutic application. Gold nanoparticles are used frequently to delivery certain drugs into large tissues in the body, and now with SWNTs coupled with proteins we are just steps away from revolutionizing current molecular therapies. Grigoryan calls it the “SWNT/protein/gold nanoparticle sandwich.”

 

In case that was not enough, Grigoryan wanted to produce his own functional protein. He developed a membrane protein with the ability to transport zinc ions into the cell. Using his program, he developed a symmetrical protein that can bind to zinc and carry the ion into the cell in an energetically favorable process. His lab tested the idea using artificial membranes made from lipid vesicles impermeable to zinc but contained the protein.  They showed that, by adding their synthetic zinc transporter ions, zinc ions could be pumped across the membrane.

 

Overall, Grigoryan has made great contributions to the fields of bioengineering and computationally. While generating entire organisms may seem farfetched at this early stage, the work of individuals such as Grigoryan, nevertheless, makes this exciting prospect ever more of a possibility.