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Scientists use computer modelling of protein to cure epilepsy and heart disease

This finding opens up new prospects for developing new-generation pharmaceuticals

MOSCOW, January 19. /TASS/. Scientists from the Higher School of Economics (HSE) and The Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS (IBCh RAS) modeled the structure of a protein which blocks potassium channels, said the HSE press-service. This finding opens up new prospects for developing new-generation pharmaceuticals.

"We analyzed the models of the protein, Tk-hefu2, to study its ability to inhibit potassium channels. Our results form a basis for designing new highly-efficient blockers/modulators of potassium channels," said Alena Likhonosova, one of the authors of the research and a graduate of the HSE’s master program in Mathematical Methods of Modeling and Computer Technologies.

Potassium channels are protein structures (which the human body has about 40 various types of them) that are built into the cell membrane and involved in various physiological processes. Through these channels, the ions migrate ensuring the "communication" of cells with the external world. Disturbances in the function of potassium channels cause the appearance of neurodegenerative, cardiovascular, and other diseases. A deep understanding of the working principles of potassium channels facilitates the development of medical drugs to cope with epilepsy, cardiac arrhythmia, and many other diseases.

Proteins have a very complex 3D-structure which plays an important role in their functioning. In order to create new drugs, it is of particular importance to unravel how these channels work at a molecular level, that is to define the structures of key proteins involved in the sub-processes. To solve this task, Likhonosova utilized a computer method of molecular dynamics which bounces the atoms like pool balls in billiards and enables the construction of stable configurations virtually. Supervised by Professor Roman Efremov, she completed the study in the Laboratory of Modeling Biomolecular Systems at IBCh RAS and devised a model of the spatial structure of the previously synthesized protein, Tk-hefu2.

As a starting point, the models of similar peptides were utilized. The point mutations were introduced to construct new models of the two most frequent states of the protein, Tk-hefu2. The results of computer simulations proved that only one of those two states is biologically active and capable of inhibiting potassium channels. The study was carried out purely with mathematical tools, without longstanding and expensive biological experiments.

It is this state of Tk-hefu2 one should use as a basis for new artificial peptides-mutants, the prototypes of drugs which will manage to be selectively bound to their targets in a cell, the molecules of potassium channels. This approach in modern biomedicine assuming target-focusing action at a molecular level should replace the traditional treatment with its "massive chemical attacks" to the body.