BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: protein structure

“Secret Doors” Are Not So Secret Anymore! 

In AP Biology class, we learned that an allosteric interaction is when an effector (some other kind of molecule) inhibits or activates an enzyme at its allosteric site. When an allosteric enzyme binds to an effector molecule, a conformational change occurs. The allosteric effects of many mutations that cause diseases, such as cancer drivers, cause them to be pathological. Allosteric sites are very difficult to locate because the rules governing how proteins work at the atomic level are hidden out of sight.

EnzymeActiveandAllostericSites

A recent discovery reveals newly discovered “secret doors” that control protein function and which could potentially be targeted in order to improve the conditions of cancer, dementia, and infectious diseases. Proteins play a crucial role in all living organisms by fighting diseases, speeding up reactions, acting as messengers, etc. A protein’s structure is essential to its function, and with one change in its sequence if amino acids could result in devastating consequences to a human’s health. 

Researchers have previously found success in targeting active sites, and now, with this new method, allosteric sites are identifiable as well. Several treatments have been designed that target a protein’s active site; however, active sites of different proteins look very similar, causing medications to bind and inhibit many different proteins at once. This leads to potential side effects. In contrast, allosteric drugs are one of the most effective medications available today due to the specificity of allosteric sites. The new method in targeting allosteric sites has been used to chart the first map ever of these allosteric sites in two of the most common human proteins. This new approach may be a game changer for drug discovery, leading to more effective medications, and enabling researchers to locate and exploit vulnerabilities in any protein—even those previously thought to be untreatable! 

Please feel free to leave your thoughts or questions in the comments! 🙂

AlphaFold: Is Artificial Intelligence Taking Over?

In this news article by  she talks about a new deep-learning artificial intelligence system called AlphaFold. The purpose of this new technology is to predict the 3-D shapes of proteins by recognizing patterns in structures. At its first release in 2021, the AlphaFold included predictions for most known human proteins, with predictions of over 350,000 protein structures. Since its initial release, the AlphaFold database has increased the number of protein structure predictions to over 200 million.

Confidence alphafoldAF-Q63HQ2-F1

As you can see by the model, some parts of the prediction are more or less accurate than others. One of the main issues with AlphaFold is the fact that these are only predictions. Scientists cannot use this information with full confidence and require further experiments to be able to be confident in the findings. Even with this issue, scientists and researchers have been able to develop potential new vaccines, improve their understanding of diseases, and gain insight into human evolution with this new artificial intelligence system.

As you may remember from your AP Biology class, protein structures are extremely important in allowing the protein to perform its job. Proteins are extremely integral in your body’s ability to function. Enzymes are used to speed up reactions, antibodies protect our body from diseases, hormones send signals to the body, etc.  By knowing the structure of the protein, scientists gain a better understanding of how proteins and all of these processes work. Just by changing one amino acid, the whole structure changes which can cause diseases such as Sickle Cell Anemia. If you would like to learn more about other important purposes of protein structure, this article goes into more in-depth on the applications of protein structure and modeling.

Now onto the topic of artificial intelligence as a whole. While artificial intelligence can reduce human error, take risks instead of humans, create unbiased decisions, and automate repetitive actions, it also has several downsides(besides the possibility of it becoming sentient and taking over the world like in movies). Some of these are having high costs, increasing the amount of unemployment, being emotionless, having no morals, and making humans lazier. Artificial intelligence has the potential to completely change society as a whole. I believe that as long as we are able to keep artificial intelligence under control and not let it get into the wrong hands, it will be a great benefit to society through important breakthroughs, such as AlphaFold, and new ideas that would have never been thought of without the use of this technology.

Do you believe artificial intelligence will be the salvation for humanity or will it be its downfall?

Could Sharks be the Solution to Ineffective SARS-CoV-2 Antibody Treatments?

Sharks are often associated with gruesome stories of attacks and horror. However, lead researcher at the University of Wisconsin-Madison School of Medicine and Public Health, Dr. Aaron LeBeau believes sharks deserve to be recognized in a more positive light– due to their potential for creating advanced neutralizing antibodies (NAb) therapeutics for treating SARS-CoV-2.

Ginglymostoma cirratum bluffs

Neutralizing antibodies have demonstrated efficacy in treating SARS-CoV-2 in previous trials. In the recent past, the FDA authorized two NAb therapeutics for emergency use for SARS-CoV-2. However, the effectiveness of these two treatments has been complicated by the development of new variants with highly mutated target antigens. These naturally occurring mutations in the target antigen result in insufficient neutralization of the virus when using those current therapeutics derived from classical human antibodies. 

This is news for concern as genome sequencing exposed the virus to create two single-letter mutations each month

As we learned in our AP Biology class, mutations to proteins such as SARS-CoV-2 antigens occur within the amino acid chains in the protein’s primary structure. These changes in chemicals could alter the kinds of covalent or ionic bonds in the protein’s tertiary structure. This, of course, changes the antigen’s three-dimensional shape. This is why the original NAbs have experienced diminished performance as new variants emerged. The antibodies from the treatments simply could no longer recognize the virus’ new antigen structure.

Therefore, there is a dire need for the development of new, more specialized NAbs, that can recognize the newly mutated epitopes that are currently incompatible with current neutralizing antibody therapeutics.

Dr. Aaron LeBeau believes that key findings for creating more efficient NAb treatments could be derived from the likes of nurse sharks! Within the immune systems of sharks, antibody-like proteins called Variable New Antigen Receptors (VNARs) were found to be highly effective at neutralizing coronaviruses, according to his recent publication in the Nature Communications journal.

Due to the small and highly specialized structure, VNARs are able to access and bind to epitopes that human antibodies normally couldn’t. This superior ability allows VNARs to reach deep into pockets and grooves within the target antigen, allowing for a better fit and neutralization. Dr. LeBeau’s research team concluded that their data suggests that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, such as the Delta and Omnicron variants. 

With the help from researchers from the University of Minnesota and the Scottish biotech company, Elasmogen, the team hopes to develop the shark antibodies for therapeutic use within 10 years.

Do you think this is promising news? How do you feel about using shark “antibodies” in place of our own for serious cases of SARS-CoV-2? Assuming it’s safe, effective, and accessible to you, would you accept this treatment if you contracted a serious case of SARS-CoV-2? Please leave your thoughts in the comments.

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