Holding a mirror to life’s key molecules

Illustration of chemical molecules superimposed over sketched hands.

Enlarge / The left- and right-handed forms of an amino acid. Every living thing uses the left-handed form exclusively. (credit: Wikimedia Commons)

The central dogma of molecular biology holds that DNA gets transcribed into RNA, which then gets translated into proteins. Of course, there are exceptions—some viruses, like coronaviruses, forego DNA altogether and encode their genetic information in RNA genomes. Other viruses, like HIV, have RNA genomes that must be copied into DNA and then transcribed back into RNA before being made into proteins. But as a general rule, “DNA to RNA to protein” describes how information moves within cells.

A unique property of biological molecules is that they have handedness. Naturally occurring molecules occur in roughly equal mixtures of left- and right-handed varieties. This means that molecules can have identical atoms and shapes but cannot be superimposed one upon the other. Instead, they are mirror images of each other, like our right and left hands.

(This can be difficult to envision, which is why pre-meds taking organic chemistry in college spend so much time playing with those ball-and-stick molecular models.)

Read 9 remaining paragraphs | Comments

#biochemistry, #biology, #chirality, #dna, #proteins, #rna, #science

Google turns AlphaFold loose on the entire human genome

Image of a diagram of ribbons and coils.

Enlarge (credit: Sloan-Kettering)

Just one week after Google’s DeepMind AI group finally described its biology efforts in detail, the company is releasing a paper that explains how it analyzed nearly every protein encoded in the human genome and predicted its likely three-dimensional structure—a structure that can be critical for understanding disease and designing treatments. In the very near future, all of these structures will be released under a Creative Commons license via the European Bioinformatics Institute, which already hosts a major database of protein structures.

In a press conference associated with the paper’s release, DeepMind’s Demis Hassabis made clear that the company isn’t stopping there. In addition to the work described in the paper, the company will release structural predictions for the genomes of 20 major research organisms, from yeast to fruit flies to mice. In total, the database launch will include roughly 350,000 protein structures.

What’s in a structure?

We just described DeepMind’s software last week, so we won’t go into much detail here. The effort is an AI-based system trained on the structure of existing proteins that had been determined (often laboriously) through laboratory experiments. The system uses that training, plus information it obtains from families of proteins related by evolution, to predict how a protein’s chain of amino acids folds up in three-dimensional space.

Read 14 remaining paragraphs | Comments

#ai, #biochemistry, #biology, #computer-science, #protein-folding, #science

Google details its protein-folding software, academics offer an alternative

Image of two multi-colored traces of complex structures.

Enlarge (credit: University of Washington)

Thanks to the development of DNA-sequencing technology, it has become trivial to obtain the sequence of bases that encode a protein and translate that to the sequence of amino acids that make up the protein. But from there, we often end up stuck. The actual function of the protein is only indirectly by its sequence. Instead, the sequence dictates how the amino acid chain folds and flexes in three-dimensional space, forming a specific structure. That structure is typically what dictates the function of the protein, but obtaining it can require years of lab work.

For decades, researchers have tried to develop software that can take a sequence of amino acids and accurately predict the structure it will form. Despite this being a matter of chemistry and thermodynamics, we’ve only had limited success—until last year. That’s when Google’s DeepMind AI group announced the existence of AlphaFold, which can typically predict structures with a high degree of accuracy.

At the time, DeepMind said it would give everyone the details on its breakthrough in a future peer-reviewed paper, which it finally released yesterday. In the meantime, some academic researchers got tired of waiting, took some of DeepMind’s insights, and made their own. The paper describing that effort also was released yesterday.

Read 17 remaining paragraphs | Comments

#ai, #biochemistry, #biology, #deepmind, #google, #protein-folding, #science, #software

Dozens of viruses seem to use a different DNA base

Image of two chemical structures.

Enlarge / Normal DNA uses adenine (left), while some viruses use diaminopurine instead.

DNA is the genetic material used by every living organism. But, in a few edge cases, the four bases of DNA—adenine, thymidine, cytosine, and guanine—undergo chemical modifications. And in viruses, things are far more flexible, with many using RNA instead of DNA as their genetic material. In all these cases, the base pairing in the genetic material takes place according to the rules that James Watson and Francis Crick first proposed.

Until now, there was a single exception, a virus that infects bacteria and uses its own, seemingly unique base. But researchers have finally looked in more detail, and they’ve discovered that this “Z-DNA” seems to be used by dozens of viruses.

Not that Z

Confusingly, there’s something else called Z-DNA. The DNA in our cells has a right-handed curve, called A-DNA, to its double helix. But it’s also possible to have a double helix with a left-handed curve, called Z-DNA.

Read 15 remaining paragraphs | Comments

#biochemistry, #biology, #chemistry, #dna, #science

Scientists create new class of “Turing patterns” in colonies of E. coli

Scientists have shown how a new class of Turing patterns work by using synthetic biology to create them from scratch in the lab.

Shortly before his death, Alan Turing published a provocative paper outlining his theory for how complex, irregular patterns emerge in nature—his version of how the leopard got its spots. These so-called Turing patterns have been observed in physics and chemistry, and there is growing evidence that they also occur in biological systems. Now a team of Spanish scientists has managed to tweak E. coli in the laboratory so that the colonies exhibit branching Turing patterns, according to a recent paper published in the journal Synthetic Biology.

“By using synthetic biology, we have a unique opportunity to interrogate biological structures and their generative potential,” said co-author Ricard Solé of Universitat Pompeu Fabra in Barcelona, Spain, who is also an external professor at the Santa Fe Institute. “Are the observed mechanisms found in nature to create patterns the only solutions to generate them, or are there alternatives?” (Synthetic biology typically involves stitching together stretches of DNA—which can be found in other organisms, and be entirely novel—and inserting into an organism’s genome.)

In synthetic biology, scientists typically stitch together long stretches of DNA and insert them into an organism’s genome. These synthesized pieces of DNA could be genes that are found in other organisms or they could be entirely novel.

Read 11 remaining paragraphs | Comments

#biochemistry, #biophysics, #e-coli, #physics, #science, #symmetry-breaking, #synthetic-biology, #turing-patterns

Researchers make their own enzyme pathway to get CO₂ out of the air

Researchers make their own enzyme pathway to get CO₂ out of the air

Enlarge (credit: Olivier Le Moal | Getty Images)

Before this century is over, we’re almost certainly going to need to pull massive amounts of carbon dioxide back out of the atmosphere. While we already know how to do carbon capture and storage, it takes a fair amount of energy and equipment, and someone has to pay for all that. It would be far more economical to pull CO2 out of the air if we could convert it to a useful product, like jet fuel. But processes like that also take a lot of energy, plus raw materials like hydrogen that take energy to create.

Plants and a huge range of microbes successfully pull carbon dioxide out of the air and use it to produce all sorts of complicated (and valuable!) chemicals. But the pathways they use to incorporate CO2 aren’t very efficient, so they can’t fix enough of the greenhouse gas or incorporate it into enough product to be especially useful. That has led a lot of people to look into re-engineering an enzyme that’s central to photosynthesis. But a team of European researchers has taken a radically different approach: engineering an entirely new biochemical pathway that incorporates the carbon of CO2 into molecules critical for the cell’s basic metabolism.

Sounds good in theory

On the rare occasions that most biologists think about biochemical pathways, energy is an afterthought. Most cells have enough of it to spare that they can afford to burn through their own energy supplies to force rather improbable pathways forward to get the chemicals they want. But grabbing carbon out of the atmosphere represents a very different sort of problem. You want it to happen as a central part of the cell’s metabolism rather than a pathway out on the periphery so that you grab a lot of carbon. And you want it to happen in a way that’s more efficient than the options the cells already have.

Read 16 remaining paragraphs | Comments

#biochemistry, #biology, #carbon, #carbon-dioxide, #catalysis, #science, #synthetic-biology

DeepMind AI handles protein folding, which humbled previous software

Proteins rapidly form complicated structures which had proven difficult to predict.

Enlarge / Proteins rapidly form complicated structures which had proven difficult to predict. (credit: Argonne National Lab / Flickr)

Today, DeepMind announced that it has seemingly solved one of biology’s outstanding problems: how the string of amino acids in a protein folds up into a three-dimensional shape that enables their complex functions. It’s a computational challenge that has resisted the efforts of many very smart biologists for decades, despite the application of supercomputer-level hardware for these calculations. DeepMind instead trained its system using 128 specialized processors for a couple of weeks; it now returns potential structures within a couple of days.

The limitations of the system aren’t yet clear—DeepMind says it’s currently planning on a peer-reviewed paper and has only made a blog post and some press releases available. But the system clearly performs better than anything that’s come before it, after having more than doubled the performance of the best system in just four years. Even if it’s not useful in every circumstance, the advance likely means that the structure of many proteins can now be predicted from nothing more than the DNA sequence of the gene that encodes them, which would mark a major change for biology.

Between the folds

To make proteins, our cells (and those of every other organism) chemically link amino acids to form a chain. This works because every amino acid shares a backbone that can be chemically connected to form a polymer. But each of the 20 amino acids used by life has a distinct set of atoms attached to that backbone. These can be charged or neutral, acidic or basic, etc., and these properties determine how each amino acid interacts with its neighbors and the environment.

Read 13 remaining paragraphs | Comments

#ai, #biochemistry, #biology, #computational-biology, #computer-science, #deepmind, #protein-folding, #science

Chitin could be used to build tools and habitats on Mars, study finds

A figurine of an astronaut stands next to a block.

Enlarge / Scientists mixed chitin—an organic polymer found in abundance in arthropods, as well as fish scales—with a mineral that mimics the properties of Martian soil to create a viable new material for building tools and shelters on Mars. (credit: Javier G. Fernandez)

Space aficionados who dream of one day colonizing Mars must grapple with the stark reality of the planet’s limited natural resources, particularly when it comes to building materials. A team of scientists from the Singapore University of Technology and Design discovered that, using simple chemistry, the organic polymer chitin—contained in the exoskeletons of insects and crustaceans—can easily be transformed into a viable building material for basic tools and habitats. This would require minimal energy and no need for transporting specialized equipment. The scientists described their experiments in a recent paper published in the journal PLOS ONE.

“The technology was originally developed to create circular ecosystems in urban environments,” said co-author Javier Fernandez. “But due to its efficiency, it is also the most efficient and scalable method to produce materials in a closed artificial ecosystem in the extremely scarce environment of a lifeless planet or satellite.”

As we previously reported, NASA has announced an ambitious plan to return American astronauts to the Moon and establish a permanent base there, with an eye toward eventually placing astronauts on Mars. Materials science will be crucial to the Artemis Moon Program’s success, particularly when it comes to the materials needed to construct a viable lunar (or Martian) base. Concrete, for instance, requires a substantial amount of added water in order to be usable in situ, and there is a pronounced short supply of water on both the Moon and Mars. And transport costs would be prohibitively high. NASA estimates that it costs around $10,000 to transport just one pound of material into orbit. 

Read 7 remaining paragraphs | Comments

#artemis-moon-program, #biochemistry, #biology, #biomimicry, #chitin, #mars, #materials-science, #nasa, #science, #space-colonization

Researchers find a chemical that makes locusts swarm

Image of a person fleeing from a cloud of locust.

Enlarge (credit: NOAA)

The year 2020 may be one for the record books in terms of apocalyptic tidings. In addition to the usual background of fires, floods, and earthquakes, the plague is still around. And you might have heard something about a pandemic. But what really nails down the apocalyptic vibe is the fact that the year has seen swarms of locusts causing the sorts of problems they’re famous for.

In a tiny bit of good news, the same sort of research that may bail us out with therapies and a vaccine for SARS-CoV-2 could potentially help us out against future locust swarms. That’s because a team of biologists based in China has now identified the chemical that calls locusts to swarm and shown that genetic engineering can eliminate the response.

A lot of evidence

There’s nothing especially exciting about any single aspect of the research here. Instead, the researchers simply put together techniques from a variety of specializations and then applied them to the topic of locust swarms. Locusts are normally solitary animals, but they become immensely destructive when conditions induce them to form massive swarms that are big enough to be picked up by radar. In addition to the altered behavior, swarming locusts actually look physically different, indicating that the decision to swarm involves widespread changes to a locust’s biology.

Read 9 remaining paragraphs | Comments

#biochemistry, #biology, #locusts, #pheromones, #science

Mutation may be helping the coronavirus spread more readily

Cartoon image of the virus, showing its spike proteins.

Enlarge (credit: State of Delaware)

About a month ago, news reports painted a potentially grim picture: a single mutation in SARS-CoV-2 was taking over the world, rapidly displacing earlier forms of the virus in most locations. The researchers behind the finding suggested we were watching in real time as SARS-CoV-2 was evolving into a form that spreads more readily within human populations.

While the evidence was suggestive, it wasn’t decisive, and there were a number of alternative explanations for the pattern of viral spread. As is so often the case in science, we needed more data. Now, some additional data has arrived in the form of a draft paper that suggests that there’s a biochemical reason for why the mutated form of the virus might be more potent.

Scientific back and forth

The idea behind the original results was fairly simple. If we assume that mutations show up at random in the coronavirus genome, then the chance of two identical mutations appearing independently in the virus’s genome is pretty low, given that the genome is over 30,000 bases long. Thus, if we see the same mutation in two different locations, the chances are very good that they got there through common descent from an ancestor that had the mutation.

Read 11 remaining paragraphs | Comments

#biochemistry, #biology, #coronavirus, #covid-19, #sars-cov-2, #science, #virology

Researchers engineer photosynthetic bacteria to produce hydrogen

Image of strings of small green cells

Enlarge (credit: State of Oklahoma)

The price of photovoltaic power has plunged, making it competitive with fossil fuel-powered electrical generation. But there is still a range of applications, like ships and aircraft, where electrical power doesn’t help much. And storing the electricity produced by solar power so that it can be used at night remains an unsolved problem. For those reasons, there’s been continued interest in converting solar power to a fuel that can be stored, either through the use of electricity generated by photovoltaics or by using light to directly power fuel generation.

There’s obviously a means of generating fuel through light that’s been in use for roughly 3 billion years: photosynthesis. But photosynthesis requires a large and complex suite of proteins that’s hard to maintain outside of cells. And inside of cells, the products of photosynthesis are quickly put to use to help the cells grow. So, engineering a version of photosynthesis that might be useful for fuel production has been challenging.

Earlier this week, however, researchers from the University of Kiel described how they’ve rearranged some photosynthetic proteins to make bacteria that emit hydrogen when exposed to light.

Read 11 remaining paragraphs | Comments

#biochemistry, #bioengineering, #biofuels, #biology, #cyanobacteria, #hydrogen, #photosynthesis, #renewable-energy, #science

First drug known to work against SARS-CoV-2 imaged in action

Complex diagram showing the location of many molecules in the RNA copying process.

Enlarge / The RNA being copied is in dark blue; the copy is in turquoise; the enzyme is in pale green; and the drug is in pink.

Just this week, we had the first promising report of a drug that appears to improve the recovery time of patients suffering from COVID-19. Hot on the heels of that announcement, a scientific journal has released a paper that describes how the drug interferes with the virus. While there’s no real surprises in what has been revealed, it provides key details of how SARS-CoV-2 can be blocked.

Copying machine

Targeting a virus with a drug is a challenge. Viruses make their living by using their host’s proteins to do most of the work of making new viruses. That means a drug has to target some of the few proteins encoded by the virus while not interfering with any of the far more prevalent host cell proteins. In the case of coronavirus, biologists have identified a number of distinct features of the virus that may be targeted without an obvious risk of causing severe side effects.

Remdesivir, which saw a large clinical trial produce promising results, is a drug that’s designed to target one of these virus-specific vulnerabilities. The coronavirus genome is encoded using the chemical RNA, as opposed to the DNA used for our genome. In fact, there’s nothing about our cells that requires them to make an RNA copy of an RNA molecule. As a result, the coronavirus genome encodes proteins that do this RNA-to-RNA copying, called an RNA-dependent RNA polymerase. Remdesivir was designed to look like one of the building blocks of RNA in the hope that it would bind to an RNA virus’ polymerase and inhibit it.

Read 12 remaining paragraphs | Comments

#biochemistry, #biology, #coronavirus, #covid-19, #drug-development, #remdesivir, #sars-cov-2, #science, #structural-biology

Newly engineered enzyme can break down plastic to raw materials

Image of plastic bottles.

Enlarge (credit: Orange County NC )

Plastics have a lot of properties that have made them fixtures of modern societies. They can be molded into any shape we’d like, they’re tough yet flexible, and they come in enough variations that we can tune the chemistry to suit different needs. The problem is that they’re tough enough that they don’t break down on their own, and incinerating them is relatively inefficient. As a result, they’ve collected in our environment as both bulk plastics and the seemingly omnipresent microplastic waste.

For natural materials, breaking down isn’t an issue, as microbes have evolved ways of digesting them to obtain energy or useful chemicals. But many plastics have only been around for decades, and we’re just now seeing organisms that have evolved enzymes to digest them. Figuring they could do one better, researchers in France have engineered an enzyme that can efficiently break down one of the most common forms of plastic. The end result of this reaction is a raw material that can be reused directly to make new plastic bottles.

An unwanted PET

The plastic in question is polyethylene terephthalate, or PET. PET has a variety of uses, including as thin films with very high tensile strength (marketed as mylar). But its most notable use is in plastic drink bottles, which are a major component of environmental plastic waste. First developed in the 1940s, the first living organism that can break down and use the carbon in PET was described in 2016—found in sediment near a plastic recycling facility, naturally.

Read 12 remaining paragraphs | Comments

#biochemistry, #biology, #green, #plastics, #recycling, #science