DSA Faculty
API
← к списку преподавателей

Ефремов Роман Гербертович

Московский институт электроники и математики им. А.Н. Тихонова

Профиль на hse.ru ↗ тел.: +7 (495) 916-88-76 | 15129 | +7 (903) 743-16-56
Публикаций
127
Языков
2
Наград
5
Конференций
3
Профиль Публикации (127) Курсы (4)

Профессиональные интересы

Вычислительная биологиякомпьютерная биологиямолекулярное моделированиеструктура и динамика биомолекулбиофизика

Должности

  • Профессор — Московский институт электроники и математики им. А.Н. Тихонова, Департамент прикладной математики

Био

  • · Начал работать в НИУ ВШЭ в 2013 году.
  • · Научно-педагогический стаж: 42 года.

Образование

  • 2007 · Ученое звание: Профессор
  • 2000 · Доктор физико-математических наук
  • 1986 · Кандидат физико-математических наук
  • 1983 · Специалитет: Московский инженерно-физический институт, специальность «Дозиметрия и защита», квалификация «Инженер-физик»

Награды и поощрения

  • · Участие в научных советах и обществах: член Ученого Совета ИБХ РАН; член трех специализированных диссертационных советов (ИБХ РАН, МГУ, ГУ НИИ БМХ РАМН); член Американского химического общества; член Биофизического общества (США).
  • · Надбавка за публикацию в журнале из Списка А (и приравненном к нему научном издании) (2025–2026, 2024–2025, 2023–2024)
  • · Надбавка за публикацию в международном рецензируемом научном издании (2022–2023, 2021–2022, 2019–2021)
  • · Надбавка за статью в зарубежном рецензируемом журнале (2014–2016)
  • · Надбавка за статью в зарубежном рецензируемом научном издании (2016–2018)

Гранты и проекты

  • 2016 · Грант Российского научного фонда «Компьютерный анализ структурно-функциональных аспектов олигомеризации трансмембранных доменов рецепторов сигнальных систем клетки», 2014-2016 гг., руководитель.
  • 2016 · Грант Российского научного фонда «Молекулярные технологии управления нейросигнализацией», 2014-2016 гг., отв. соисполнитель.
  • 2017 · Грант Программы Президиума РАН «Молекулярная и клеточная биология», тема: «Молекулярное моделирование пептидов и белков в мембранах как фундаментальная основа для рационального конструирования новых биологически активных соединений», 2013-2017 гг., руководитель.
  • 2014 · Грант Программы Президиума РАН № 27 «Основы фундаментальных исследований нанотехнологий и наноматериалов», тема: «Новые вычислительные технологии мультимасштабного моделирования мезоскопических биомембранных систем: от понимания фундаментальных принципов структурно-динамического поведения – к созданию наноструктур для биомедицинских приложений», 2012-2014 гг., руководитель.
  • 2015 · Грант РФФИ «Коллективные молекулярные движения, кластеры и флуктуации в гидратированных липидных бислоях и их роль в структурно-динамическом поведении клеточных мембран», 2013-2015 гг., руководитель.
  • 2018 · Грант РФФИ «Клеточные мембраны как стохастические динамические системы: от атомистического моделирования – к рациональному конструированию новых мембранных материалов», 2016-2018 гг., руководитель.

Конференции (3)

Показать все
  • · 2016: Актуальные вопросы биологической физики и химии БФФХ-2016 (Севастополь). Доклад: Оценка влияния среды на димеризацию трансмембранных доменов гликофорина А в компьютерном эксперименте
  • · 2016: Khujand Symposium on Computational Materials and Biological Sciences 2016 (Худжанд). Доклад: Helix-helix interactions in membranes: focus on lipids
  • · 2014: Dushanbe Symposium on Computational Materials and Biological Sciences DSCMBS-2014 (Душанбе). Доклад: The adaptable lipid matrix promotes transmembrane helices association in membranes

Идентификаторы исследователя

Публикации (127)

Role of dimerization efficiency of transmembrane domains in activation of fibroblast growth factor receptor 3

2013 · ARTICLE · en

Mutations in transmembrane (TM) domains of receptor tyrosine kinases are shown to cause a number of inherited diseases and cancer development. Here, we use a combined molecular modeling approach to understand molecular mechanism of effect of G370R and A391E mutations on dimerization of TM domains of human fibroblast growth factor receptor 3 (FGFR3). According to results of Monte-Carlo conformational search in the implicit membrane and further molecular dynamics simulations, TM dimer of this receptor is able to form a number of various conformations, which differ significantly by the free energy of association in a full-atom model bilayer. The aforementioned mutations affect dimerization efficiency of TM segments and lead to repopulation of conformational ensemble for the dimer. Particularly, both mutations do not change the dimerization free energy of the predominant (putative “non-active”) symmetric conformation of TM dimer, while affect dimerization efficiency of its asymmetric (“intermediate”) and alternative symmetric (putative “active”) models. Results of our simulations provide novel atomistic prospective of the role of G370 and A391E mutations in dimerization of TM domains of FGFR3 and their consecutive contributions to the activation pathway of the receptor.

Chugunov A.O., Koromyslova A.D., Berkut A.A., Peigneur S., Tytgat J., Polyansky A.A., Modular Organization of α-Toxins from Scorpion Venom Mirrors Domain Structure of Their Targets - Sodium Channels

2013 · ARTICLE · en

To gain success in the evolutionary “arms race”, venomous animals such as scorpions produce diverse neurotoxins selected to hit targets in the nervous system of prey. Scorpion α-toxins affect insect and/or mammalian voltage-gated sodium channels (Nav’s) and thereby modify the excitability of muscle and nerve cells. Although more than a hundred α-toxins are known and a number of them have been studied into detail, the molecular mechanism of their interaction with Nav’s is still poorly understood. Here, we employ extensive molecular dynamics simulations and spatial mapping of hydrophobic/hydrophilic properties distributed over the molecular surface of α-toxins. It is revealed that in spite of the small size and relatively rigid structure, these toxins possess modular organization from structural, functional and evolutionary perspectives. The more conserved and rigid “core module” is supplemented with the “specificity module” (SM) that is comparatively flexible and variable, and determines the taxon (mammal vs. insect) specificity of α-toxin activity. We further show that SMs in mammal toxins are more flexible and hydrophilic than in insect toxins. Concomitant sequence-based analysis of Nav’s extracellular loops suggests that α-toxins recognize the channels using both modules. We propose that the core module binds to the voltage-sensing domain of repeat IV, whereas the more versatile SM interacts with the pore domain in repeat I of Nav’s. These findings corroborate and expand the hypothesis on different functional epitopes of toxins that has been reported previously. In effect, we propose that the modular structure in toxins evolved to match the domain architecture of Nav’s.

Lipid-II forms potential “landing terrain” for lantibiotics in simulated bacterial membrane

2013 · ARTICLE · en

Bacterial cell wall is targeted by many antibiotics. Among them are lantibiotics, which realize their function via interaction with transmembrane lipid-II molecule — a chemically conserved part of the cell wall synthesis pathway. To investigate structural and dynamic properties of this molecule, we have performed a series of nearly microsecond-long molecular dynamics simulations (MD) of lipid-II and some of its analogs in zwitterionic single component and charged mixed model phospholipid bilayers (the reference and mimic of the bacterial plasmatic membrane, respectively). Extensive analysis revealed that lipid-II forms a unique “amphiphilic pattern” exclusively on the surface of the model bacterial membrane (and not in the reference bilayer). We hypothesize that conserved features of lipid-II along with characteristic modulation of the bacterial membrane provide a recognition spot for many lantibiotics. This putative recognition mechanism opens new opportunities for studies on lantibiotics action and design of novel armament against resistant bacterial strains.

Interaction between the elastin peptide VGVAPG and human elastin binding protein

2013 · ARTICLE · en

The elastin binding protein (EBP), a spliced variant of lysosomal β-galactosidase, is the primary receptor of elastin peptides that have been linked to emphysema, aneurysm and cancer progression. The sequences recognized by EBP share the XGXXPG consensus pattern found in numerous matrix proteins, notably in elastin where the VGVAPG motif is repeated. To delineate the elastin binding site of human EBP, we built a homology model of this protein and docked VGVAPG on its surface. Analysis of this model suggested that Gln-97 and Asp-98 were required for interaction with VGVAPG because they contribute to the definition of a pocket thought to represent the elastin binding site of EBP. Additionally, we proposed that Leu-103, Arg-107, and Glu-137 were essential residues because they could interact with VGVAPG itself. Site-directed mutagenesis experiments at these key positions validated our model. This work therefore provides the first structural data concerning the interaction of the VGVAPG with its cognate receptor. The present structural data should now allow the development of EBP-specific antagonists.

PDF ↗

A single missence mutation in a coiled-coil domain of Escherichia coli ribosomal protein S2 confers thermo-sensitive phenotype that can be suppressed by ribosomal protein S1

2013 · ARTICLE · en

Ribosomal protein S2 is an essential component of translation machinery, and its viable mutated variants conferring distinct phenotypes serve as a valuable tool in studying the role of S2 in translation regulation. One of a few available rpsB mutants, rpsB1, shows thermosensitivity and ensures enhanced expression of leaderless mRNAs. In this study, we identified the nature of the rpsB1 mutation. Sequencing of the rpsB1 allele revealed a G-to-A transition in the part of the rpsB gene which encodes a coiled-coil domain of S2. The resulting E132K substitution resides in a highly conserved site, TKKE, a so-called N-terminal capping box, at the beginning of the second alpha helix. The protruding coiled-coil domain of S2 is known to provide binding with 16S rRNA in the head of the 30S subunit and, in addition, to interact with a key mRNA binding protein, S1. Molecular dynamics simulations revealed a detrimental impact of the E132K mutation on the coiled-coil structure and thereby on the interactions between S2 and 16S rRNA, providing a clue for the thermosensitivity of the rpsB1 mutant. Using a strain producing a leaderless lacZ transcript from the chromosomal lac promoter, we demonstrated that not only the rpsB1 mutation generating S2/S1-deficient ribosomes but also the rpsA::IS10 mutation leading to partial deficiency in S1 alone increased translation efficiency of the leaderless mRNA by about 10-fold. Moderate overexpression of S1 relieved all these effects and, moreover, suppressed the thermosensitive phenotype of rpsB1, indicating the role of S1 as an extragenic suppressor of the E132K mutation.

PDF ↗

Dynamic clustering of lipids in hydrated two-component membranes: results of computer modeling and putative biological impact.

2013 · ARTICLE · en

Delineation and analysis of lateral clustering of lipids in model bilayers is an important step toward understanding of the physical processes underlying formation of lipid domains and rafts in cell membranes. Computer modeling methods represent a powerful tool to address the problem since they can detect clusters of only few lipid molecules – this issue still resists easy characterization with modern experimental techniques. In this work, we propose a computational method to detect and analyze parts of membrane with different packing densities and hydrogen bonding patterns. A series of one- and two-component fluid systems containing lipids with the same polar heads and different acyl chains, dioleoylphosphatidylcholine (18:1) and dipalmitoylphosphatidylcholine (16:0), or with same acyl chains and different polar heads, dioleoylphosphatidylserine (18:1) and dioleoylphosphatidylcholine (18:1), were studied via molecular dynamics simulations. Four criteria of clustering were considered. It was shown that the water-lipid interface of biomembranes represents a highly dynamic and “mosaic” picture, whose parameters depend on the bilayer composition. Some systems (e.g., with 20-30% of the anionic lipid) demonstrate unusual clustering properties and demand further investigation at molecular level. Lateral microheterogeneities in fluid lipid bilayers seem to be among the most important factors determining the nature of the membrane-water interface in a cell.

DOI ↗ PDF ↗

Cobra cardiotoxins: membrane interactions and pharmacological potential

2013 · ARTICLE · en

Natural polycationic membrane-active peptides typically lack disulfide bonds and exhibit fusion, cell-penetrating, antimicrobial activities. They are mostly unordered in solution, but adopt a helical structure, when bound to phospholipid membranes. Structurally different are cardiotoxins (or cytotoxins, СTs) from cobra venom. They are fully b-structured molecules, characterized by the three-finger fold (TFF). Affinity of CTs to lipid bilayer was shown to depend on amino acid sequence in the tips of the three loops. In the present review, CT-membrane interactions are analyzed through the prism of data on binding of the toxins to phospholipid liposomes and detergent micelles, as well as their structural and computational studies in membrane mimicking environments. We assess different hydrophobicity scales to compare membrane partitioning of various CTs and their membrane effects. A comparison of hydrophobic/hydrophilic properties of CTs and linear polycationic peptides provides a key to their biological activity and reveal rationality for design of new membrane-interacting compounds. Finally, since the viewpoint of the data obtained on model lipid membranes, cytotoxic activity of CTs against cancer cells is discussed.

PDF ↗

Курсы (4)