computational biology

Researchers from the University of Washington’s Institute of Protein Design have created a new method to engineer protein dimers, or pairs. Working alongside molecular biologists at Ohio State, the researchers have made it possible “to design proteins so they come together exactly how you want them to,” as the paper’s lead author explains.

Two proteins held together by DNA.

Before, researchers relied on DNA to engineer dimeric proteins, utilizing complementary strands to create helical proteins held together by the hydrogen bonds between base pairs. However, DNA-created proteins lack the functionality of highly active proteins like protease, while also being prone to interference during synthesis. So, longing to create these more complex protein assemblies, the researchers engineered a new way to make them.

Using a computer program called Rosetta, the researchers designed hydrogen bond networks for their desired protein complexes, creating complementary bond networks for each pair of amino acids. For this, Rosetta algorithmically determined the ideal shape of each amino acid chain, calculating the best way to balance out intermolecular forces and finding the resulting lowest energy level, the most probable state for each chain. Thus, the researchers could accurately design complementary protein structures, so the two parts would fit together exactly.

As a result, the researchers were able to create highly specific, more active protein dimers that form double helices unencumbered by DNA and do not form unwanted shapes or interfere with other proteins during synthesis.

This new method has the potential to “transform biomedical technology”, as scientists can now have much more control over protein interactions, potentially engineering bacteria to produce energy or designing protein machines to diagnose diseases, among many other tasks. As the researchers set their sights on more complicated, dynamic protein complexes, there is no telling what exciting discoveries await.

Nervous Tissue

A recent project from the National Institute of Health aims to build a 3D map of human tissues on a cellular level. Known as HuBMAP (Human BioMolecular Atlas Program), the project is largely seen as a successor to the Human Genome Project and will likely yield similarly incredible results.

With the goal of better understanding how cells organize and cooperate in tissues, the researchers involved in the project hope to be able to view the body with molecular level precision, understanding which “genes and proteins are activated in each part of the body” and the effects that has. Although it won’t map the entire body, the project will nevertheless present many challenges in dealing with big data, a very current issue in science research, as the researchers seek to map trillions of cells, compose high-resolution maps of them, and categorize those maps.

Caltech, one of the few institutions chosen for the program, is working on mapping the circulatory system, analyzing differences in the tissues of arteries, veins, and other components on a microscopic scale. Using a new imaging technique known as seqFISH, researchers at CalTech aim to analyze mRNA and in doing so pinpoint thousands of biomarkers across tissues in 3D.

In creating such a detailed and complex atlas of tissue maps, researchers hope to answer big questions in pathology and aging with one particular goal being to better understand how healthy tissues vary on a cellular level. As the project continues into the mid-2020s, one can only hope that HuBMAP enables us to fill critical gaps in our knowledge of cells, tissues, and health.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: computational biology

Programming protein pairs

NIH program to create 3D map of human tissues

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