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Computer Modelling Used to Create New Generation Medicines

Structure and Dynamics of α-hairpinin Peptide Tk-hefu2 in Water: Computer Simulations, an article in which HSE researchers make discoveries relevant to a variety of fields, including mathematics, information science, physics, and biology, opens up new opportunities for medicines to arise that regulate the function of potassium channels that ensure the vital functioning of human cells.

Potassium channels are membrane proteins that are involved in various physiological processes. It is through these channels (of which the human body has around 40 types) that ions flow, allowing the body’s cells to ‘communicate’ with the outside world.

When potassium channels do not function correctly, this can lead to the development of neurodegenerative and cardiovascular diseases, to name a few. A deep understanding of how these channels work is essential in developing innovative medicines to fight epilepsy, cardiac arrhythmia, and many other pathological conditions.

In order to create the medicines, it is important to know how the channels are regulated at the level of individual molecules; that is, it is important to decipher previously unknown molecular mechanisms in the channels’ functioning and determine the structure of the key proteins that participate in these processes.

The most progressive way to do this is through computer modelling. Alena Lihonosova, a graduate of HSE’s master’s programme in Mathematical Methods of Modelling and Computer Technologies, used computer modelling to construct a model of the bioengineered α-hairpinin peptide Tk-hefu2, the spatial structure had been unsolved.

The research took place in the Biomolecular Systems Modelling Laboratory of the Russian Academy of Science’s Institute of Bioorganic Chemistry under the supervision of Professor Roman Efremov. In the study, Lihonosova used the molecular dynamics computer simulation method, which tracks roughly 107 atoms simultaneously and allows for stable configurations to be created from them virtually.

At the beginning of the study, models of similar peptides were used. Certain changes — point mutations — were purposefully directed towards the peptides, and as a result new models were constructed of two major conformational states of Tk-hefu2 in water.

The results of the computer experiments showed that only one of the two states was biologically active and able to block the functioning of the potassium channels. This was done partly mathematically without any long or expensive biology experiments.

It is this state in particular that should be used as the basis for new artificial mutant peptides and prototype drugs that will be able to selectively act on its own targets within a cell, i.e., on potassium channel molecules. This is an approach in contemporary biomedicine that implies targeted action at the molecular level instead of traditional treatments that involve ‘massive chemical attacks’ on the body.

January 19, 2017