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Supercomputer technologies of atomic modeling in the material science and physics of biomembranes

Priority areas of development: engineering science
2019

Goal of research:

  • research of the performance, energy consumption and efficiency of new and promising computing hardware
  • development of the original parallel algorithms and application of programming technologies to increase the performance or portability of computing codes
  • monitoring and statistical analysis of the load of supercomputers to develop recommendations for more efficient use
  • research of metastable and extreme states of matter
  • build of viscosity models of liquid hydrocarbons and mixtures with predictive power
  • study of glass transition processes, including metal glasses
  • search for new biologically active compounds acting on biomembranes and membrane proteins and revealing the molecular mechanism of their functioning
  • development of a promising peptide with antimicrobial activity that interacts with lipid-II in the bacterial membrane, the determination of the molecular aspects of recognition of the target by a lantibiotic nisin
  • issues of selectivity of peptide blockers of ion channels from natural poisons

Methodology:

  • To evaluate the characteristics of the supercomputer, artificial tests and model bencharks based on real-life problems are used. Telegraf and Grafana were used for load analysis of supercomputers; the initial data for analysis was obtained through three monitoring technologies RAPL, IPMI and SNMP. To improve the portability of the LAMMPS package, the ROCm HIP hybrid programming platform was used.
  • Materials science uses molecular dynamics with a wide range of potentials, including specific ClayFF, COMPAS, OPLS, ReaxFF, as well as modeling a quantum structure based on the density functional theory in software packages VASP and CP2K.
  • In biological studies, homology modeling, molecular dynamics with parameterizations for biological systems (Gromos 43a2, Amber), and the de novo protein structure prediction using the molecular hydrophobic potential method were used

Empirical base of research:

Performance tests (benchmarks) were performed on the new HSE supercomputer, on Desmos and Fisher clusters, including nodes with an immersion cooling system. In biological studies, the experimental results of the IBC laboratory were used.

Results of research:

Performance tests of the new HSE supercomputer were performed to evaluate the basic characteristics and performance on real-life computational programs, including classical molecular dynamics and calculation of the electronic structure. Interconnect tests have shown Infiniband EDR's advantage in terms of bandwidth and packet size greater than 8 KB in MPI exchanges. In terms of the latency, the new supercomputer is inferior to the Desmos cluster, on which our team previously conducted such tests. The minimum latency time is 0.92 μs. We try the simultaneous launch of different types of load (GPU or CPU) tasks on the nodes, e.g. VASP and machine learning tasks on 4 nodes. It is shown that this approach can increase the overall efficiency of resource use while reducing the performance of each individual calculation.

A new AMD ROCm HIP portable hybrid computing programming platform was reviewed and tested. Using this platform the laboratory prepares to use the promising computing systems in 2021. In the framework of the study, the universal molecular dynamics package LAMMPS was ported to this platform. In addition to improving portability, it increases the performance on AMD hardware by ~ 5% due to the reduction in overhead that is present at OpenCL.

The same monitoring and analytics systems for power and energy consumption were implemented on three types of computing nodes: an air-cooled hybrid supercomputer, and air-cooled and liquid-cooled CPU segments of Fisher cluster. Testing using a model example of a molecular-dynamic problem shows the excess consumption of an air-cooled system compared to an average 30% or 1.4 kW compared to immersion cooling of the system. We found a minimum of total energy consumption for the test task on the CPU system. The study of the code of the network subsystem of the BeeGFS file system made it possible to identify prospects for its optimization and processing using an optimized library for working with various networks.

Quantum-mechanical modeling of heated dense hydrogen showed a wide range of metastable states in the temperature range from 700 to 1000 K. The presence of these metastable states may cause discrepancies between experiments on determining the hydrogen phase diagram in shock wave experiments and in static measurements in diamond anvils. The atomistic modeling method was used to study the viscosity of liquid hydrocarbons and mixtures. Mixing rules are obtained that allow one to evaluate the viscosity of mixtures from the viscosity of pure substances, which is important for modeling hydrocarbon formations. Using a complex anharmonic model of interactions COMPASS, the viscosity of a hydrocarbon was calculated up to a pressure of 10 thousand atm. Up to pressures of 6 thousand atm. the results are consistent with experimental measurements within 2%. The data obtained allow us to talk about the predictive capabilities of modeling in the problems of determining the properties of materials. Based on molecular dynamics and Monte Carlo calculations, confirmation of the theory of percolation is obtained as applied to a network of hydrogen bonds in liquid and supercritical water. It was found that the number of hydrogen bonds in a water molecule obeys a binomial distribution in a much wider range of temperatures and densities than previously assumed. In molecular-dynamic calculations, the processes of glass aging and the effects of annealing and periodic thermal effects on the properties of the amorphous state are studied. It is shown that thermal effects can both reduce and increase the energy of glass. Annealing with the application of external voltage can lead to the accumulation of regions with a nonequilibrium structure, in contrast to classical annealing, in which the structure passes to a more equilibrium state.

Molecular details of protein-protein and protein-lipid interactions are described for a number of critical cell receptors: the ErbB family, insulin receptor, glycophorin A, neuraminidase-1. It is shown that point mutations and membrane properties both affect the stability and functioning of membrane receptors. Based on these points, we propose an “interceptor” peptide prototype to modulate neuraminidase-1 dimerization.

A “trap” configuration is described for nisin fragment as a crucial step for lipid II recognition in membranes which can be useful for further novel antibiotics design.

We developed a novel peptide Tk-hefu 2 targeting Kv 1.3 channels – a good example of rational design of biologically active compound.

Publications:


Efremov R. Dielectric-dependent strength of interlipid H-bonding in biomembranes: a model case study. // Journal of Chemical Information and Modeling. 2019. Vol. 59. No. 6. P. 2765-2775. doi
Efremov R., Bennasroune A., Romier-Crouzet B., Sébastien B., Laffargue M., Martiny L., Maurice P., Duca L. Elastic Fibers and Elastin Receptor Complex: Neuraminidase-1 takes the center stage. // Matrix Biology. 2019. Vol. 84. P. 57-67. doi
Bocharov E. V., Nadezhdin K. D., Urban A. S., Volynsky P. E., Pavlov K. V., Efremov R., Arseniev A. S., Bocharova O. V. Familial L723P Mutation Can Shift the Distribution between the Alternative APP Transmembrane Domain Cleavage Cascades by Local Unfolding of the Ε‑Cleavage Site Suggesting a Straightforward Mechanism of Alzheimer’s Disease Pathogenesis. // ACS Chemical Biology. 2019. Vol. 14. No. 7. P. 1573-1582. doi
Efremov R., Нольде Д. Е., Волынский П. Е., Захарова Г. С., Palmer R. A., Tonevitsky A. Specific refolding pathway of viscumin A chain in membrane-like medium reveals a possible mechanism of toxin entry into cell. // Scientific Reports. 2019. Vol. 9. No. 413. P. 1-12. doi
Pouvreau M., Greathouse J. A., Cygan R. T., Kalinichev A. G. Structure of Hydrated Kaolinite Edge Surfaces: DFT Results and Further Development of the ClayFF Classical Force Field with Metal-O-H Angle Bending Terms // Journal of Physical Chemistry C. 2019. Vol. 123. P. 11628-11638. doi
Loganathan N., Bowers G. M., Ngouana-Wakou B. F., Kalinichev A. G., Kirkpatrick R. J., Yazaydin A. O. Understanding Methane/Carbon Dioxide Partitioning in Clay Nano- and Meso-Pores with Constant Reservoir Composition Molecular Dynamics Modeling // Physical Chemistry Chemical Physics. 2019. Vol. 21. P. 6917-6924 . doi
Kirova E. M., Pisarev V. The glass transition criteria for aluminum–copper melt // Journal of Physics: Conference Series. 2019. Vol. 1147. No. 012014. P. 1-5. doi
Трофимов Ю. А., Krylov N., Efremov R. Confined dynamics of water in transmembrane pore of TRPV1 ion channel // International Journal of Molecular Sciences. 2019. Vol. 20. No. 4285. P. 1-13. doi
Tabakmakher V. M., Krylov N., Kuzmenkov A. I., Efremov R., Vassilevski A. A. Kalium 2.0, a comprehensive database of polypeptide ligands of potassium channels // Scientific data. 2019. Vol. 6. No. 73. P. 1-8. doi
Норман Г. Э., Писарев В. В., Флейта Д. Ю. Особенность в точке перехода от равновесной к метастабильной фазе металлического расплава // Письма в Журнал экспериментальной и теоретической физики. 2019. Т. 109. № 10. C. 689-693. doi
Pisarev V., Mistry S. Volume-based mixing rules for viscosities of methane + n-butane liquid mixtures // Fluid Phase Equilibria. 2019. Vol. 484. P. 98-105. doi
Polyansky A. A., Bocharov E. V., Velghe A. I., Kuznetsov A. S., Bocharova O. V., Urban A. S., Arseniev A. S., Zagrovic B., Demoulin J., Efremov R. G. Atomistic mechanism of the constitutive activation of PDGFRA via its transmembrane domain // Biochimica et Biophysica Acta - General Subjects. 2019. Vol. 1863. No. 1. P. 82-95. doi
Priezjev N., Makeev M. Structural transformations during periodic deformation of low-porosity amorphous materials // Modelling and Simulation in Materials Science and Engineering. 2019. Vol. 27. P. 025004-025004. doi
Priezjev N., Liu Qinglong The influence of complex thermal treatment on mechanical properties of amorphous materials // Computational Materials Science. 2019. Vol. 161. P. 93-98. doi
Priezjev N., Makeev M. The influence of periodic shear on structural relaxation and pore redistribution in binary glasses // Journal of Non-Crystalline Solids. 2019. Vol. 506. P. 14-20. doi
Priezjev N. The potential energy states and mechanical properties of thermally cycled binary glasses // Journal of Materials Research. 2019. Vol. 34. No. 15. P. 2664-2671. doi
Stegailov V., Dlinnova E., Ismagilov T., Khalilov M., Kondratyuk N., Makagon D., Semenov A., Simonov A., Smirnov G., Timofeev A. Angara interconnect makes GPU-based Desmos supercomputer an efficient tool for molecular dynamics calculations // International Journal of High Performance Computing Applications. 2019. Vol. 33. No. 3. P. 507-521. doi
Timofeev A. Divergence of dust particles trajectories in dusty plasma model // Journal of Physics: Conference Series. 2019. Vol. 1147. No. 012100. P. 1-6. doi
Timofeev A., Nikolaev V. S. Influence of ion shadowing effect on average inter-particle distance in dusty plasma crystals // Journal of Physics: Conference Series. 2019. Vol. 1147. No. 012109. P. 1-7. doi
Timofeev A., Nikolaev V. S. Inhomogeneity of a harmonically confined Yukawa system // Physics of Plasmas. 2019. Vol. 26. No. 073701. P. 1-8. doi
Myshkin M., Mannikko R., Krumkacheva O., Kulbatskii D., Chugunov A., Berkut A., Paramonov A., Shulepko M., Fedin M., Hanna M., Kullmann D., Bagryanskaya E., Arseniev A., Kirpichnikov M., Lyukmanova E., Vassilevski A., Shenkarev Z. Cell-Free Expression of Sodium Channel Domains for Pharmacology Studies. Noncanonical Spider Toxin Binding Site in the Second Voltage-Sensing Domain of Human NaV1.4 Channel // Frontiers in Pharmacology. 2019. Vol. 10. P. 1-20. doi
Berkut A., Chugunov A., Mineev K., Peigneur S., Tabakmakher V., Krylov N., Oparin P., Лихоносова А. Ф., Novikova E., Arseniev A., Grishin E., Tytgat J., Efremov R., Vassilevski A. Protein Surface Topography as a tool to enhance the selective activity of a potassium channel blocker // Journal of Biological Chemistry. 2019. Vol. 294(48). P. 18349-18359. doi
Волынский П. Е., Гаврилина А. М., Нольде Д. Е., Ефремов Р. Г. Выявление факторов важных для транслокации белков через мембрану методами компьютерного моделирования, in: II объединенный научный форум: VI съезд физиологов СНГ, VI съезд биохимиков России, IX российский симпозиум «Белки и пептиды» (Сочи, Дагомыс, 1–6 октября 2019). Научные труды. Москва : Издательство "Перо", 2019. С. 141-141. 
Urban A., Bocharov E. V., Nadezhdin K., Pavlov K., Shtykova E., Tikhaia E., Volynsky P. E., Efremov R., Arseniev A. S., Bocharova O. V. Conformational variability and intramembrane recognition possibly associated with abnormal cleavage of APP transmembrane domain, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 299-299. 
Osmakov D., Belozerova O., Koshelev S., Andreev Y., Dubinnyi M., Efremov R., Chugunov A., Kublitski V., Kozlov S. Mode of action and biological activity of sevanol and its analogues on acid-sensing ion channels, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 183-183. 
Bocharov E. V., Lesovoy D. M., Pavlov K., Bocharova O. V., Urban A. S., Mineev K. S., Bershacky Y., Shtykova E., Volynsky P. E., Efremov R., Arseniev A. S. Structural basis of the signal transduction via transmembrane domains of type I receptors in norma and pathology, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 130-130. 
Ефремов Р. Г. Путешествия в «аномальные зоны» клетки с помощью вычислительной биофизики, in: Сборник научных трудов VI съезда биофизиков России. Краснодар : Кубанский государственный университет, 2019. С. 16-17. 
Бочаров Э., Лесовой Д., Минеев К., Бочарова О., Урбан А., Бершацкий А., Надеждин К., Волынский П., Ефремов Р. Г., Арсеньев А. Роль белок-липидных взаимодействий в функционировании битопных мембранных белков, in: II объединенный научный форум: VI съезд физиологов СНГ, VI съезд биохимиков России, IX российский симпозиум «Белки и пептиды» (Сочи, Дагомыс, 1–6 октября 2019). Научные труды.. Москва : Издательство "Перо", 2019. С. 45-46. 
Ефремов Р. Г. Технология «динамического молекулярного портрета» в вычислительном анализе белков и биомембран, in: II объединенный научный форум: VI съезд физиологов СНГ, VI съезд биохимиков России, IX российский симпозиум «Белки и пептиды» (Сочи, Дагомыс, 1–6 октября 2019). Научные труды.. Москва : Издательство "Перо", 2019. С. 58-58. 
Коншина А. Г., Крылов Н. А., Ефремов Р. Г. Механизм встраивания мембрано-активного цитотоксина в липидный бислой: моделирование in silico, in: Сборник научных трудов VI съезда биофизиков России. Краснодар : Кубанский государственный университет, 2019. С. 160-161. 
Zamaletdinov M. F., Kuznetsov A., Maurice P., Efremov R. Dimerization of transmembrane domain of insulin receptor: structure and possible role in activation, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 262-262. 
Albrecht C., Dhaideh Z., Appert-Collin A., Dauchez M., Blaise S., Romier-Crouzet B., Kuznetsov A., Efremov R., Duca L., Gueroult M., Maurice P., Bennasroune A. Effects of interfering transmembrane peptides on neuraminidase-1 activity, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 295-296. 
Kuznetsov A., Maurice P., Efremov R. Protein–lipid interactions in glycophorin-like dimerization motifs of transmembrane helices, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 268-269. 
Кузнецов А. С., Ефремов Р. Г. Димеризация трансмембранных доменов белков: роль липидного окружения, in: Тезисы докладов XXVI Международной конференции "Математика. Компьютер. Образование". МКО-2019., 2019. С. 45-45. 
Кузнецов А. С., Bennasroune A., Maurice P., Ефремов Р. Г. Молекулярно-динамические аспекты взаимодействия трансмембранного сегмента нейраминидазы-1 с перспективным пептидным перехватчиком, in: II объединенный научный форум: VI съезд физиологов СНГ, VI съезд биохимиков России, IX российский симпозиум «Белки и пептиды» (Сочи, Дагомыс, 1–6 октября 2019). Научные труды.. Москва : Издательство "Перо", 2019. С. 108-108. 
Кузнецов А. С., Ефремов Р. Г. Роль мембранного окружения в процессе димеризации трансмембранных сегментов рецепторных тирозинкиназ семейства ErbB, in: Сборник научных трудов VI съезда биофизиков России. Краснодар : Кубанский государственный университет, 2019. С. 165-165. 
Panina I., Chugunov A., Dmitry N., Efremov R. Nisin/lipid II interaction in bacterial membrane: molecular dynamics study, in: FEBS Open Bio Volume 9, Issue S1 Supplement: 44th FEBS Congress, From Molecules to Living Systems, Krakow, Poland, July 6‐11, 2019. Oxford : Wiley, 2019. С. 269-269. 
Панина И. С., Чугунов А. О., Крылов Н. А., Нольде Д. Е., Ефремов Р. Г. Фармакофорная модель распознавания низином липида II в бактериальной мембране, in: Сборник научных трудов VI съезда биофизиков России. Краснодар : Кубанский государственный университет, 2019. С. 83-84. 
Чугунов А. О., Панина И. С., Ефремов Р. Г. Антимикробные пептиды, нацеленные на липид II мембран бактерий: ключевой принцип действия, in: II объединенный научный форум: VI съезд физиологов СНГ, VI съезд биохимиков России, IX российский симпозиум «Белки и пептиды» (Сочи, Дагомыс, 1–6 октября 2019). Научные труды.. Москва : Издательство "Перо", 2019. С. 60-60. 
Loganathan N., Yazaydin A. O., Bowers G. M., Ngouana-Wakou B. F., Kalinichev A. G., Kirkpatrick R. J. Role of cations in the methane/carbon dioxide partitioning in nano- and mesopores of illite using constant reservoir composition molecular dynamics simulation // Journal of Physical Chemistry C. 2020. Vol. 124. P. 2490-2500. doi
Тимофеев А. В., Семенов В. П., Николаев В. С. Неоднородность структурных и динамических характеристик пылевой плазмы в газовом разряде // Журнал экспериментальной и теоретической физики. 2020. Т. 157. № 1. C. 180-188. doi
Кузнецов А. С., Ефремов Р. Г. Оценка взаимного влияния белок-мембрана для рецепторных тирозинкиназ в компьютерном эксперименте, in: Математика. Компьютер. Образование. Тезисы.. Ижевск : Ижевский институт компьютерных исследований, 2020. С. 53-54. 
Efremov R., Коншина А. Г., Дубовский П. В. Stepwise insertion of cobra cardiotoxin CT2 into a lipid bilayer occurs as an interplay of protein and membrane “dynamic molecular portraits” // Journal of Chemical Information and Modeling. 2021. Vol. 61. No. 1. P. 385-399. doi