Spare parts might 'jump-start' design of artificial proteins

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November 5, 2017 00:25

Scientists at the Wezimann Institute will continue their experiments, building antibodies based on those of camels and llamas.

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Weizmann Institute of Science.

Weizmann Institute of Science.. (photo credit:MICHAEL JACOBSON/WIKIMEDIA COMMONS)

The concept of proteins that can be designed on computers for specific functions has been a cutting-edge concept that has obstinately remained “in the future.” New research recently published in the Proceedings of the National Academy of Science (PNAS) and carried out at the Weizmann Institute of Science in Rehovot may bring that future a bit closer.

By going back to evolution – nature’s drawing board – the scientists have created new proteins based on “existing natural parts” that carry out their intended function with flying colors. The research was conducted by Dr. Sarel Fleishman, research students Dror Baran, Maria Gabriele Pszolla, Gideon Lapidoth and colleagues at Weizmann’s biomolecular sciences department.

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In Sarel’s lab, proteins are designed with computer- based programs that enable them to generate new structures – for example, antibodies or enzymes – that do not exist in nature. If they want a protein that will perform a specific action, such as binding to another protein or carrying out a chemical reaction, they can compute from beginning to end the genetic sequence that will line up amino acids in the proper order and cause the protein to fold into the correct three-dimensional shape. Such proteins could, at least in theory, usher in a new age of custom-designed drugs and catalysts, but the challenges of planning of large biological molecules are immense.

The group focused their attention on some parts of natural antibodies or enzymes that don’t make it into the computer designs that start from scratch – particularly structures called “loops,” which are inherently unstable and “non-ideal” and therefore challenging when it comes to computational prediction. These “non-ideal” loops can be often be found at the very center of the active regions – those that recognize a target or bind to or cleave another molecule.

To incorporate these parts, the researchers decided to design a functioning antibody from existing parts, rather than building one from scratch. They broke the structures found in natural antibodies down into segments, including the loops and other supporting features. In effect, the researchers tinkered with readymade parts, similar to the way evolution works.

Natural evolution is obviously a very slow process; a new family of antibodies can take tens of millions of years to appear. So the researchers went back to the computerized planning process, this time armed with their new insight. The new designs were then tested experimentally in the lab, a few dozen new antibodies at a time.

Initially, the designs performed poorly, but through five design-build-test cycles, the researchers uncovered some general rules for designing antibodies. In essence, they created a sort of symbiotic evolution – they design programs evolving along with the experimental tests, each pushing the other forward. They created artificial antibodies that targeted insulin and characterized these molecules down to the resolution of single atoms.

In future experiments, the team will design artificial antibodies modeled on those of camels and llamas.

While a human antibody or one from any number of common animals has 200 amino acids, in camels and llamas they are made of just 100 and are stable and effective. This could make the design and production of artificial antibodies for human conditions more efficient and have relevance for designing new diagnostics and therapeutics.

Forget fingerprint computer identification or retinal scanning. A University at Buffalo team has developed a computer security system using the dimensions of your heart as your identifier. The system uses low-level Doppler radar to measure your heart and then continually monitors your heart to make sure no one else has stepped in to run your computer.

Fortunately, the system is a safe and potentially more effective alternative to passwords and other biometric identifiers, they claim. It may eventually be used for smartphones and at airport screening barricades.

“We would like to use it for every computer because everyone needs privacy,” said computer science Prof. Wenyao Xu, the study’s lead author. “Logging-in and logging-out are tedious,” he said. The signal strength of the system’s radar is much less than Wi-Fi, and therefore does not pose any health threat, Xu said.

“We are living in a Wi-Fi-surrounding environment every day, and the new system is as safe as those Wi-Fi devices,” he said. The reader is about five milliwatts, even less than 1% of the radiation from our smartphones.”

The system needs about eight seconds to scan a heart the first time, and thereafter the monitor can continuously recognize that heart. The system, which was three years in the making, uses the geometry of the heart, its shape and size and how it moves to make an identification. “No two people with identical hearts have ever been found,” Xu said. And people’s hearts do not change shape, unless they suffer from serious heart disease.

Heart-based biometrics systems have been used for almost a decade, primarily with electrodes measuring electrocardiogram signals, “but no one has done a non-contact remote device to characterize our hearts’ geometry traits for identification,” he said.

The new system has several advantages over current biometric tools, like fingerprints and retinal scans, Xu said. First, it is a passive, non-contact device, so users are not bothered with authenticating themselves whenever they log in. It also monitors users constantly, preventing a computer from working if a different person is in front of it. Therefore, people do not have to remember to log off when away from their computers.

Xu plans to miniaturize the system and have it installed onto the corners of computer keyboards. The system could also be used for user identification on cell phones. For airport identification, a device could monitor a person up to 30 meters away.


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