Acceleration of protein docking calculations
A new method for calculating protein interactions will accelerate drug development
Biologists and mathematicians from MIPT, Stony Brook University and other research centers have taught a computer to predict the structure of protein "couplings" in a cell 10 times faster. The work of Padhorny et al. Protein–protein docking by fast generalized Fourier transforms on 5D rotational manifolds is published in the journal Proceedings of the National Academy of Sciences of the USA.
"The new approach makes it possible to model protein interactions at the genome level. This will lead to a better understanding of how our cells function and will allow us to develop drugs for diseases caused by "erroneous" protein interactions," says Dmitry Kozakov, professor at Stony Brook University and associate professor at MIPT.
A matter of technique
In order to obtain one that exists in the real world from all possible variants of the arrangement of two large molecules relative to each other, scientists solve the following problem: two proteins with a known structure are given. It is necessary to predict what their "docking" will look like. This is the so-called rigid docking method, when the structure of the elements is set and it is necessary to assemble an advantageous configuration from them. In scientific terminology, such a task is called "protein-protein docking".
In the new algorithm, proteins are described in a system of radial-spherical coordinates, which in itself is as close as possible to the shape of the protein. This makes it possible to divide proteins into "functional blocks" and solve the problem in a simpler form.
At first glance, the task seems simple and understandable: to assemble such a structure of proteins is a matter of technique, almost the same as assembling a children's constructor. But, according to scientists, if we draw an analogy with the same "Lego", the computational complexity of such an operation can be compared with the compilation of all possible pairs of 10,000 initial blocks of the constructor.
The real structure of the protein complex together with an ensemble of alternative structures selected using a new algorithm. Source: provided by the author of the article
The idea of the researchers was to present proteins as a combination of "quantum surfaces" – some blocks described by the mathematical apparatus of quantum mechanics. This approach allows us to simultaneously calculate the interaction of many pairs of protein sites with each other, rather than evaluating each pair independently. The new method can work up to 100 times faster than the best of the existing ones, while remaining accurate. According to scientists, such a program "counts" 15 minutes on a personal computer and is a serious alternative to experimental methods for determining protein interactions.
The new algorithm will soon become part of the popular ClusPro automatic protein-protein interaction calculation system. The resource, previously developed by the authors of the article, today has more than 15,000 users worldwide. At the last competition among CAPRI (Critical Assessment of PRotein Interactions) protein structure determination specialists, the ClusPro server was recognized as the best automatic system for calculating protein–protein interaction.
"Thousands of different protein interactions are carried out in an ordinary cell. Explaining these interactions helps to describe important processes: the work of the body as a whole and the methods of treatment of certain diseases (for example, cancer)," Dmitry Kozakov comments on the study.
The co-authors of the article are also Andrey Kazennov, a graduate student at MIPT, and Dmitry Podgorny, a graduate of the MIPT Master's degree and a graduate student at Stony Brook University.
The research was supported by grant 14.A18.21.1973 of the Ministry of Education and Science of the Russian Federation.
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21.07.2016