Nanotechnology Discovery Saves Lives

 

 

Quick read

New medicines that save lives by combating drug-resistant bacteria —such as Staph (Staphylococcus aureus) —are just one of the results of the largest biological simulation ever.

 

 

Nanoscience—the study of things of "little" importance, one might quip—led to the largest biological simulation ever, which helped Los Alamos scientists decode genetic information. The methodology paved the way for developing new antibiotics and modeling the entire protein synthesis process—a process crucial to saving lives.

The body comprises enumerable nanofactories called ribosomes that work overtime to keep us alive. In each of our trillions of cells, a million ribosomes create proteins—chains of amino acids—that are the basis of life. A quintillion protein factories rebuild our entire body every seven years.

Ribosome study is nothing new but, "only now we can use supercomputers to investigate, in atomic detail, how this very complex machine really works," says Los Alamos National Laboratory theoretical biologist Kevin Sanbonmatsu. "It has been the holy grail and now our team at Los Alamos is making it happen."

Sanbonmatsu and Theoretical Biology and Biophysics Group Leader Chang-Shung Tung created the first atomic-level computer model of a single ribosome.

Sanbonmatsu and his team hope their 3D simulations can solve conflicting interpretations about ribosomes. Secondly, this technology will provide information required to design new medicine to combat drug-resistant bacteria, such as the prevalent Staph (Staphylococcus aureus), which causes many diseases and fatal infections such as food poisoning.

The Molecular-Dynamics Code

A ribosome's base parts were a mystery not too long ago, until 2000 when researchers solved the 3D atomic-level structure of each of the ribosome's two subunits. This research inspired Sanbonmatsu and Tung, who fit these asymmetrical subunits into a single mathematical representation and built a computer code to represent how the constituent atoms and molecules interact. They soon used their simulation work to find the tRNA's route into the rat's nest of the ribosome.

Their first model was the largest biomolecular-dynamics simulation ever done, encompassing more than 2.5 million atoms. Sanbonmatsu was warned this project was too ambitious for a newcomer, but he disproved critics and won a federal Presidential Early Career Award for Scientists and Engineers.

Sanbonmatsu's team's simulation computed the forces among atoms to determine the path of least resistance—the minimum-energy path. Viewing the results was extraordinarily time-consuming. After months of staring at each frame, viewing every atom, he found the invisible entry channel. Only 68 of the ribosome's 5,000 amino acids interacted with tRNA during entry at a ribosomal gate; the simulation revealed the end of the tRNA with the attached amino acid was deflected to avoid the barrier and get inside the ribosome's interior. In short, the model exposed how a ribosome rejects the wrong tRNA. For the first time, researchers learned that tRNA delivered important genetic information. Additionally, this data suggests tRNA might have existed long before the ribosome, facilitating protein synthesis in pre-life systems. 

Important Nanotechnology Developments

While the origin of its name is miniscule—a billionth of a part, the core of atoms—nanotechnology is an extraordinary part of everyday life. There are some 600 commercial products available (e.g., cosmetics, sunscreen, clothing, home furnishings, sports, and electronic equipment) where nanotechnology plays a manufacturing role.

Nanoscience enables improvements in medical diagnostics and drug delivery, bioscience, chemical sensing, military platforms, and nuclear defense systems and even helped Los Alamos National Laboratory (LANL) create a supreme superconductor. Sanbonmatsu's team is also preparing a new ribosomal simulation code for Roadrunner, LANL's world's most powerful computer.