For the first time on the screen: one and a half milliseconds of folding!

At the beginning of its work, the Folding@home distributed computing project, created specifically to find a solution to the folding problem (folding a protein from a linear sequence of amino acids into a complex three-dimensional globule), set itself a 1000 times more modest task: to simulate at least one microsecond of this process.

A thousandfold increase in the folding simulation time is a huge step forward. And not from the point of view of pure science: improper folding of proteins, which is the cause of numerous diseases, including cancer and Alzheimer's disease, occurs over relatively long periods of time. Detailed, atom-accurate modeling of this process will help in the development of drugs for the prevention and treatment of many diseases.

A group of Stanford scientists coordinating the Folding@home project managed to overcome the microsecond barrier thanks to the development of a new method for dividing tasks between processors – the Markov State Model (MSM).

The video below shows one of the ways of folding the molecule of one of the proteins of the large subunit of the ribosome – NTL9. This protein was the first because normally its folding occurs very slowly (for molecular processes). On the video, these one and a half milliseconds are stretched for almost one and a half minutes.

NTL9 protein folding model in millisecond time scaleThe initial moment: the molecule is in the unfolded state.

The spiral of the secondary structure is formed very quickly,
the rest of the molecule remains in the unfolded state.
Hydrophobic collapse.
Beta structure (folded sheet structure) makes flickering movements,
An N-terminal beta hairpin is formed,
but he falls into a trap – into a "non-native" state.
 uncharacteristic contact is destroyed
A fragment with a pure secondary structure is formed.
The third part of the sheet is missing.
Attention: we are looking at the C-terminal part!
The C-terminal part shifts into place…
(repeat: pay attention to the C-terminal part again!)
...and is closed with the help of hydrogen bonds and side chains
with the formation of a twisted structure.
Folding is complete!

The results of the work are published in the Journal of the American Chemical Society: Vincent A. Voelz et al., Molecular Simulation of ab Initio Protein Folding for a Millisecond Folder NTL9(1-39).

This technique can be successfully applied for modeling in longer periods of time. Now scientists are working on further improving their method and applying it to study more complex proteins, as well as to verify numerous experimental data. The authors of the new model have already used their method to study protein folding disorders in Alzheimer's disease. Although earlier models cover a fairly wide time frame and allow us to study oligomeric fragments with a small molecular weight, the new technique promises to advance further in modeling Alzheimer's disease and establish the details of folding more complex amyloid beta oligomers than was previously possible.

A new development in the field of modeling protein folding processes is a very inspiring achievement for scientists, and they are optimistic to look for new applications of this technology.

Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Folding@Home: Molecular Simulation of ab initio Protein Folding for a Millisecond Folder19.01.2010