Electrifying science: New study describes conduction through proteins – Phys.org

17
45
Electrifying science: New study describes conduction through proteins – Phys.org
Electrifying science: New study describes conduction through proteins
A DNA polymerase–an enzyme that synthesizes DNA molecules from nucleotide building blocks–is poised between a pair of electrodes. Binding of nucleotides by the polymerase causes conductance spikes, which may be characteristic of the specific molecules bound by the polymerase.Such a device, in theory, could carry out rapid, accurate, low cost DNA sequencing, and may have many additional applications in medical diagnostics, industrial production and other areas. Credit: Lindsay lab

Amid the zoo of biomolecules essential to life, enzymes are among the most vital. Without these specialized proteins, which speed up the rates of chemical reactions, thousands of essential life processes, from cell growth and digestion to respiration and nerve function, would be impossible.

In new research, Stuart Lindsay and his colleagues investigate a recently discovered feat carried out by enzymes, and most likely, all proteins. Under proper conditions, they can act as superb conductors of electricity, permitting them to be incorporated into a range of electronic devices. “It is a way of plugging the amazing chemical diversity of enzymes directly into a computer,” Lindsay says.

While the role of protein conductance in nature remains a matter of mystery and speculation, harnessing this phenomenon for will likely open new avenues for biochemical sensing devices, smart industrial production and new innovations in medical diagnostics.

Perhaps most exciting, through a special type of enzyme may signal a significant advance for DNA sequencing. Using a DNA , nature’s own high-resolution DNA reader, in such a device could potentially allow for lightning-fast sequencing of entire human genomes with unprecedented accuracy at very low cost. The new study “opens the Pandora’s box of looking at the function of any enzyme in a computer chip.”

Current affairs

Authors of the new study describe the tricks they used to affix a DNA polymerase to a pair of electrodes and the resulting current spikes associated with the enzyme successively binding and releasing target DNA nucleotides. The successful demonstration of enzyme conductance paves the way for eventually mounting arrays of proteins onto , where they can act as biological parallel processors for a variety of tasks.

“Enzymes are incredible molecules that carry out chemical reactions that just wouldn’t happen otherwise,” Lindsay says. To give a sense of the power of these molecules, certain reactions essential to life processes, unfolding thousands of times per second, would require millennia to occur in the absence of enzymes.

Lindsay directs the Biosedign Center for Single Molecule Biophysics at Arizona State University. The center’s primary research focuses on science at the nexus of molecular medicine and nanotechnology.

His group’s findings appear in the forthcoming edition of the journal ACS Nano.

Proteins as conductors

Until quite recently, proteins were regarded strictly as insulators of electrical current flow. Now, it seems, their unusual physical properties may lead to a condition in which they are sensitively poised between an insulator and a conductor. (A phenomenon known as quantum criticality may be at the heart of their peculiar behavior.)

Indeed, in earlier research, Lindsay demonstrated strong electrical conductance through a protein captured between a pair of electrodes. The new research carries the investigations of protein conductance a step further. Previously, the protein was hooked up via its two so-called active sites. These are the regions of a protein that bind selected molecules, often resulting in a conformational change in the molecule’s complex 3-D structure and the completion of the protein’s given task.

This time, the biomolecule was sensitively wired to the electrodes by means of alternate binding sites on the enzyme, leaving the active sites available to bind molecules and carry out natural protein function.

Nature’s Kindle

The enzyme molecule chosen for the experiments is one of the most important for life. Known as a DNA polymerase, this enzyme binds with successive nucleotides in a length of DNA and generates a complimentary chain of nucleotides, one by one. This versatile nanomachine is used in living systems for copying DNA during cell replication as well as for repairing breaks or other insults to the DNA.

The study describes techniques for affixing the DNA polymerase to electrodes so as to generate strong conductance signals by means of two specialized binding chemicals known as biotin and streptavidin. When one electrode was functionalized using this technique, small conductance spikes were generated as the DNA polymerase successively bound and released each nucleotide, like a grasping hand catching and releasing a baseball. When both electrodes were outfitted with streptavidin and biotin, much stronger conductance signals, measuring 3-5 times as large, were observed.

Electrifying science: New study describes conduction through proteins
Stuart Lindsay directs the Biodesign Center for Single Molecule Biophysics. He is also a Regents’ Professor and Nadine and Edward Carson professor of physics and chemistry. Credit: Biodesign Institute at ASU

The idea for leveraging a polymerase to carry out rapid DNA sequencing has been with Lindsay for awhile. He had considered using it in earlier devices he created in which sections of DNA were fed through narrow tunnel junctions. “Wouldn’t it be neat if you could put a pair of electrodes inside of polymerases because the polymerase grabs the DNA and chugs it through the junction. If you had a readout mechanism embedded in the polymerase, you’ve got the ideal sequencing machine.”

The new method hopes to take a different approach, using the polymerase’s own speed-reading expertise to provide a readout of nucleotides through conductance spikes specific to each of the 4 DNA bases. In practice, a number of design hurdles must be overcome. Proper attachment of the polymerase for electrical conductance is a delicate affair and involved much trial and error. Binding sites must be engineered at specific domains that do not affect protein folding and function and connections had to be devised to prevent the enzyme itself from making contact with the electrodes. The use of biotin for binding the molecule also appears to be critical for high conductance. Biotin binding a pocket of the streptavidin appears to help drive electron transport deep into the protein interior, thereby maximizing conductance.

Separating conductance signals registering each successive DNA base from background noise and random motions of the contact points for the enzyme has also proven challenging and sophisticated machine learning algorithms are being brought to bear to clarify the readouts. Lindsay believes many of these noise issues will be resolved when the polymerases are incorporated into properly isolated and sealed chips holding the rigidly in place.

Enzyme frontiers

The first complete human genome was a milestone for science and medicine. The herculean effort by the Human Genome Project consumed 13 years of labor at a cost of a billion dollars. Now the floodgates to a new era of bioelectronics may be opening, with many surprises likely in store.

If remaining technical hurdles can be overcome, DNA sequencing could be carried out at the breakneck speed of a functional DNA polymerase, or around a hundred nucleotides per second. “If you put 10,000 molecules on a chip—not a hard thing to do—you’ll sequence a whole genome in under an hour,” Lindsay says



Citation:
Electrifying science: New study describes conduction through proteins (2019, October 31)
retrieved 1 November 2019
from https://phys.org/news/2019-10-electrifying-science-proteins.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

17 COMMENTS

  1. Youre so cool! I dont suppose Ive learn something like this before. So nice to search out any individual with some unique ideas on this subject. realy thanks for starting this up. this website is something that is wanted on the internet, somebody with a little bit originality. useful job for bringing one thing new to the web!

  2. This web page is known as a stroll-through for all of the data you needed about this and didn抰 know who to ask. Glimpse right here, and also you抣l positively discover it.

  3. The following time I learn a blog, I hope that it doesnt disappoint me as a lot as this one. I imply, I know it was my choice to read, but I really thought youd have something interesting to say. All I hear is a bunch of whining about one thing that you possibly can repair when you werent too busy searching for attention.

  4. There are certainly a variety of details like that to take into consideration. That is a nice point to deliver up. I provide the ideas above as basic inspiration however clearly there are questions like the one you bring up where the most important factor shall be working in trustworthy good faith. I don?t know if best practices have emerged round things like that, however I’m positive that your job is clearly identified as a fair game. Each boys and girls really feel the impression of just a moment抯 pleasure, for the remainder of their lives.

  5. I precisely had to thank you so much again. I am not sure the things I might have achieved without the ideas revealed by you regarding such concern. It became the alarming circumstance for me, but observing a new skilled manner you dealt with the issue made me to leap for delight. Extremely happy for this advice and then hope that you find out what an amazing job you’re putting in educating some other people by way of your webblog. I am certain you’ve never got to know any of us.

  6. I as well as my guys were actually reading through the good information on your website and all of a sudden I had a terrible suspicion I never thanked the website owner for them. My women happened to be absolutely warmed to see all of them and have in effect sincerely been making the most of those things. Thanks for being so considerate and also for picking out some important topics most people are really desirous to discover. My sincere regret for not expressing gratitude to earlier.

  7. I have to show my passion for your kindness for people that need assistance with your concern. Your real commitment to getting the message across had become exceedingly powerful and has always made people like me to achieve their endeavors. Your amazing valuable tutorial implies a great deal a person like me and far more to my office colleagues. Best wishes; from everyone of us.

  8. Thanks a lot for providing individuals with an extremely superb possiblity to check tips from this web site. It really is so pleasant and also stuffed with amusement for me personally and my office colleagues to visit your site at a minimum three times in 7 days to see the newest issues you will have. And definitely, I am also always motivated concerning the outstanding things you serve. Certain 1 points in this article are undoubtedly the best I have ever had.

  9. I truly wanted to send a simple word so as to say thanks to you for these precious facts you are placing at this website. My particularly long internet lookup has at the end been rewarded with useful facts to write about with my family members. I ‘d mention that many of us website visitors actually are rather lucky to be in a fine site with very many brilliant individuals with beneficial methods. I feel really privileged to have come across your entire web page and look forward to really more excellent times reading here. Thanks a lot once again for a lot of things.

  10. I have to get across my affection for your kindness in support of persons that should have assistance with in this issue. Your special dedication to getting the solution up and down had become wonderfully advantageous and have allowed regular people like me to attain their pursuits. This interesting publication indicates a whole lot to me and extremely more to my office colleagues. With thanks; from everyone of us.

  11. A lot of thanks for every one of your labor on this blog. My niece loves getting into investigation and it’s obvious why. Most people learn all concerning the powerful mode you convey good items by means of this web blog and foster contribution from website visitors on this article while my child has always been discovering a lot. Have fun with the remaining portion of the new year. Your performing a dazzling job.

  12. I truly wanted to make a quick note so as to express gratitude to you for all the great points you are giving out here. My long internet search has finally been recognized with wonderful information to go over with my contacts. I ‘d assume that many of us readers actually are very lucky to exist in a fabulous site with many outstanding individuals with valuable plans. I feel truly happy to have discovered the website page and look forward to so many more excellent moments reading here. Thanks once more for all the details.

  13. I precisely desired to say thanks yet again. I am not sure the things that I would have undertaken in the absence of the actual strategies documented by you relating to such a question. It seemed to be a fearsome difficulty in my circumstances, however , viewing a expert fashion you treated the issue forced me to jump with contentment. I’m thankful for this information as well as have high hopes you are aware of a great job that you are putting in educating others via your websites. I know that you have never got to know any of us.

LEAVE A REPLY

Please enter your comment!
Please enter your name here