{"id":620061,"date":"2026-08-04T14:42:14","date_gmt":"2026-08-04T14:42:14","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/620061\/"},"modified":"2026-08-04T14:42:14","modified_gmt":"2026-08-04T14:42:14","slug":"programmable-dna-as-molecular-glue-for-protein-crystallization","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/620061\/","title":{"rendered":"Programmable DNA as ‘molecular glue’ for protein crystallization"},"content":{"rendered":"


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\n\t\t\t\t\tAugust 4, 2026\t\t\t\t | By Mary Bailey\t\t\t<\/p>\n

For decades, scientists have largely relied on painstaking trial and error to coax proteins into crystalline forms. Crystallization enables scientists to determine the molecular structures of proteins<\/a>, which can provide a blueprint for designing drugs, engineering enzymes, and understanding disease.<\/p>\n

Now, chemists at Northwestern University<\/a> (Evanston, Illinois) have developed a new approach that replaces a tedious, unpredictable process with intentional design.<\/p>\n

In a new study published in the journal Science Advances<\/a>, Northwestern scientists repurposed flexible DNA strands as a blueprint and programmable molecular glue. Using DNA, the team directed proteins to assemble into diffraction-quality, intentionally designed crystal structures with atomic-level order. The strategy enabled the scientists to precisely control how proteins connect, creating unusually soft, flexible crystals while achieving the high structural order needed to determine protein structures.<\/p>\n

\"In<\/p>\n

In the new study, Chad Mirkin\u2019s team attached short DNA strands to each protein. Then, DNA pulled neighboring proteins together, assembling them into precisely designed crystals. The team also varied key design features \u2014 such as DNA strand length and placement \u2014 to determine how each variable affected crystal formation. Finally, they used X-ray crystallography to examine the resulting crystals. Image courtesy of the Mirkin Research Group<\/p>\n

Not only does the work simplify one of structural biology\u2019s most difficult challenges, but it also overturns a long-held assumption that flexible building blocks cannot produce crystals with atomic-level order. The approach also could enable a new generation of flexible, customizable biomaterials<\/a> for biosensing, drug delivery, bioelectronics, and robotics.<\/p>\n

\u201cThe implications of this research are profound,\u201d said Northwestern\u2019s Chad A. Mirkin, who led the study. \u201cProteins are the building blocks of life, and their structure determines their function. When we intentionally determine those structures, we gain powerful new insights into how proteins recognize other molecules, catalyze chemical reactions and interact with living systems. That knowledge ultimately helps us identify new drug targets<\/a>, design new medicines and engineer new materials.\u201d<\/p>\n

A nanotechnology pioneer, Mirkin is the George B. Rathmann Professor of Chemistry, a professor of medicine (hematology and oncology) and a professor of chemical and biological engineering, biomedical engineering and materials science and engineering at Northwestern University, where he has appointments at the Weinberg College of Arts and Sciences, Northwestern University Feinberg School of Medicine, and McCormick School of Engineering. He also is the founding director of the International Institute for Nanotechnology. Zhenyu Han, who was a graduate student in Mirkin\u2019s laboratory at the time of the study, is the paper\u2019s first author.<\/p>\n

From fighting infections to digesting food, proteins carry out nearly every essential task inside living cells. To understand how these molecular machines work \u2014 and design drugs to target them \u2014 scientists need to determine their three-dimensional structures.<\/p>\n

X-ray crystallography is the gold standard for revealing these structures. In this technique, scientists first coax billions of identical proteins to assemble into a crystal. Then, they shine X-rays through the crystal and analyze the resulting diffraction patterns to reconstruct the protein\u2019s atomic structure. But persuading proteins to form suitable crystals is often one of the most difficult and unpredictable steps in the process.<\/p>\n

To improve this unreliable step, Mirkin turned to flexible snippets of single-stranded DNA. In a 1996 study published in Nature, Mirkin and his team used complementary DNA strands to assemble gold nanoparticles into ordered structures. Since then, his lab and many others have used DNA as a programmable bonding element to organize nanoparticles, polymers and other nanoscale building blocks into ordered structures.<\/p>\n

\u201cOver 30 years ago, the Mirkin group proposed the idea to take nanoparticles and modify them with DNA to create programmable atom equivalents,\u201d Han said. \u201cNature\u2019s nanoparticles are proteins. The difference between synthetic nanoparticles and proteins is that proteins are naturally uniform and molecularly precise. So, if we modify proteins with DNA and assemble them, we can form high-quality, atomically precise crystals, overcoming a decades-old challenge in the field of DNA-programmable assembly.\u201d<\/p>\n

Normally, proteins crystallize because parts of their surfaces happen to stick together through multiple, weak chemical interactions. By contrast, Mirkin\u2019s team exploited DNA\u2019s natural tendency to seek out its perfect match. Each DNA strand is made up of four chemical \u201cletters\u201d \u2014 A, T, C and G \u2014 that pair in predictable ways. When two complementary DNA strands encounter one another, they spontaneously snap together to form the familiar double helix.<\/p>\n

In many ways, DNA bonds are more programmable than conventional chemical bonds. By changing DNA\u2019s sequence, scientists can dictate which molecules connect and where they connect. That opens the door to building crystals with customizable architectures and mechanical properties for specific applications.<\/p>\n

In the new study, Mirkin\u2019s team attached short DNA strands to each protein. DNA then pulled neighboring proteins together, assembling them into precisely designed crystals. The team also varied key design features \u2014 such as DNA strand length and placement \u2014 to determine how each variable affected crystal formation. Finally, they used X-ray crystallography to examine the resulting crystals.<\/p>\n

\u201cThe well-defined DNA-DNA interactions drove the assembly and crystallization process,\u201d Han said. \u201cAs a result, the proteins not only adopted specific positions and orientations, but the atoms within each protein are also aligned in the exact same way throughout the crystal. When that happens, you can use single-crystal X-ray diffraction methods to determine their structure and see atomic-level details within the protein.\u201d<\/p>\n

To further validate the approach, the team grew more than 1,000 protein crystals and determined the atomic structures of 28 distinct protein-DNA designs. Despite systematically changing DNA length and position, the resulting crystals consistently assembled into the designed architectures. That reproducibility, together with the direct visualization of DNA double helices linking neighboring proteins within the crystals, gave the researchers confidence that DNA \u2014 not chance \u2014 directed the assembly.<\/p>\n

\u201cThese numbers show that we didn\u2019t just get lucky,\u201d Mirkin said. \u201cWe systematically demonstrated this approach across literally hundreds of possibilities and showed over and over again that it\u2019s a reliable method. The DNA bond is a fundamentally new class of chemical bond, and this work shows how it can be used in ways that conventional chemical bonds cannot \u2014 to create a new type of material that yields new fundamental knowledge as well as technological breakthroughs that could significantly benefit society.\u201d<\/p>\n

The study was supported by the Air Force Office of Scientific Research and the National Science Foundation.<\/p>\n","protected":false},"excerpt":{"rendered":" August 4, 2026 | By Mary Bailey For decades, scientists have largely relied on painstaking trial…\n","protected":false},"author":2,"featured_media":620062,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[77],"tags":[18,19,17,163360,133],"class_list":["post-620061","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-eire","tag-ie","tag-ireland","tag-protein-engineering","tag-science"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/117037770688980782","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/620061","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=620061"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/620061\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/620062"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=620061"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=620061"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=620061"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}