?
Modeling of novel CDK7 inhibitors activity by molecular dynamics and free energy perturbation methods
Mendeleev Communications. 2020. Vol. 30. No. 4. P. 430-432.
Svitanko I., Novikov F. N., Rusina P. V., Titov I. Y., Stroylov V. S., Abdyusheva Y. R., Murlatova E. Y.
Although CDK7 inhibitors are considered to be potential anticancer drugs, all inhibitors developed so far have significant disadvantages preventing their further use. We have developed a new CDK7 inhibitor scaffold lacking hepatotoxicity using molecular dynamics (MD) and free energy perturbation (FEP/MD) methods, and were able to double its binding affinity after additional research. The combination of MD and FEP/MD methods was shown to be a valuable instrument for the development of novel and potent CDK7 inhibitors for anticancer therapy.
Priority areas:
IT and mathematics
Language:
English
Rusina P., Gandalipov E., Abdyusheva Y. et al., Cancers 2023 Vol. 15 No. 15 Article 3766
General toxicity for the organism is a major drawback of anticancer drugs. Development of new generation chemotherapeutics requires the knowledge about macromolecules critical for tumor cell viability. Among these species (called therapeutic targets), the protein kinases are the established enzymes. However, the parts of protein kinases that are supposed to be targeted by drugs can ...
Added: November 1, 2023
Omelchuk O., Malyshev V., Medvedev M. et al., Journal of Organic Chemistry 2021 Vol. 86 No. 12 P. 7975-7986
Oligomycin A is a potent antibiotic and antitumor agent. However, its applications are restricted by its high toxicity and low bioavailability. In this study, we obtained Oligomycin A Diels− Alder adducts with benzoquinone and N-benzylmaleimide and determined their absolute configurations by combining 1H and ROESY NMR data with molecular mechanics conformational analysis and quantum chemical ...
Added: September 6, 2021
Loganathan N., Bowers G. M., Yazaydin A. O. et al., Journal of Physical Chemistry C 2018 Vol. 122 No. 8 P. 4391-4402
In situ XRD and NMR experiments combined with molecular dynamics simulations using the grand canonical ensemble (GCMD) show that cation size, charge and solvation energy play critical roles in determining the interlayer expansion of smectite clay minerals when exposed to dry supercritical CO2 under conditions relevant to the earth’s upper crust, petroleum reservoirs, and geological ...
Added: May 31, 2018
Svitanko Igor, Stroylov V., Mendeleev Communications 2020 Vol. 30 No. 4 P. 419-420
Identification of disulfiram and neratinib as putative covalent inhibitors of SARS-CoV-2 virus main protease Mpro by a combination of 'on-top docking' procedure, expert evaluation of potential hits and molecular dynamics is reported herein. This finding shows the importance of further development of virtual screening add-ons. ...
Added: August 31, 2020
Loganathan N., Kalinichev A. G., Journal of Physical Chemistry C 2017 Vol. 121 P. 7829-7836
Adsorption and mobility of radioactive Cs+ isotopes in soil are among the most important factors affecting the long-term environmental footprint of nuclear accidents such as Chernobyl (1986) and Fukushima Daiichi (2011). In particular, Cs+ ions can be retained through their exchange with K+ naturally present in muscovite mica, one of the common soil mineral components. ...
Added: April 30, 2017
Aseev L. V., Chugunov A. O., Efremov R. et al., Journal of Bacteriology 2013 Vol. 195 No. 1 P. 95-104
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 ...
Added: November 14, 2013
Kiselyova N. N., Dudarev V.A., Ryazanov V. V. et al., Inorganic Materials: Applied Research 2020 Vol. 11 No. 4 P. 787-794
Compounds of compositions С+4О7 and А+2 О7 that are not yet obtained (A and B
are cations of different elements; C is Si or Ge) with a melilite-type crystal structure are predicted and their
crystal lattice parameters are evaluated. Predicting is based only on data on the properties of elements and
simple oxides. The mean accuracy of predicting ...
Added: July 29, 2020
Rebrova O., Российская ринология 2018 Т. 26 № 1 С. 65-68
Description of the statistical analysis of the data contained in original articles. Typical mistakes ...
Added: October 2, 2018
Генов П. Г., Тимербаев В. Х., Гринь А. А. et al., Нейрохирургия 2017 № 1 С. 45-53
Objective: to determine the influence of perioperative analgesia methods on the incidence of « failed back surgery syndrome» after intervertebral discal hernia removal. Material and methods: This prospective study was conducted from 2010 till 2013 and included 129 patients who underwent lumbar discectomy regarding intervertebral discal hernia. Patients of group GA+R (n=20) were operated on ...
Added: October 2, 2018
Rebrova O., Российский аллергологический журнал 2018 Т. 15 № 3 С. 25-29
The quality of the evidence on the efficacy and safety of therapeutic and preventive interventions is analyzed in health technology assessment procedure (including the development of reimbursement lists such as the List of Vital and Essential Drugs in Russian Federation) and during development of clinical guidelines. The traditional approach to assess the evidence quality is ...
Added: October 2, 2018
Medvedev M., Salikov R., Trainov K. et al., Dyes and Pigments 2019 Vol. 161 P. 500-509
Two approaches for the synthesis of D-A chromophores containing arylhydrazonocyclopentadiene acceptor moieties were developed. The first approach includes the decarboxylative azo coupling reaction between penta(methoxycarbonyl)cyclopentadienyl potassium or sodium and aryldiazonium salts to give products containing four ester groups at the acceptor moiety. The second one includes the reaction of 1,3-dimethoxycarbonyl-4,5-diphenylcyclopentadienone with arylhydrazine hydrochlorides into arylhydrazonocyclopentadienes ...
Added: October 9, 2019
Веселова Т. Н., Терновой С. К., Chepovskiy A. et al., Кардиология 2021 Т. 61 № 7 С. 28-35
Цель
Создание трехмерной математической модели коронарного кровотока по данным компьютерной томографической ангиографии (КТА) с последующим расчетом фракционного резерва кровотока (ФРККТА). Сопоставление расчетного ФРККТА с результатами инвазивных измерений.
Материалы и методы
В исследование включено 10 больных с «пограничными» (50-75%) стенозами по данным КТА, выполненной на 640-срезовом компьютерном томографе. На основании данных КТА были построены трехмерные математические модели коронарных ...
Added: August 16, 2021
М. : Энциклопедия, Инфра-М, 2018
The New Russian Encyclopedia is a fundamental reference publication in 18 volumes that characterizes nature, population, economy, history, science, art, technology and other important aspects. Contains about 60,000 articles, about 30,000 biographies, about 15,000 color illustrations, maps, charts, diagrams, tables. Leaves since 2003. ...
Added: October 28, 2018
Шелыгин Ю. А., Попов А. А., Фоменко О. Ю. et al., Российский вестник акушера-гинеколога 2018 Т. 18 № 6 С. 62-66
вить статью
Цель исследования — изучить состояние функции держания кишечного содержимого у пациенток с пролапсом гениталий. Материал и методы. Обследованы 40 пациенток с симптомами несостоятельности мышц тазового дна (пролапс органов малого таза), средний возраст — 56,6±9,5 года. Одни роды перенесли 13 (32,5%) пациенток, двое родов — 24 (60%), трое родов и более отмечались в 3 (7,5%) ...
Added: January 13, 2019
Szczerba M., Kuligiewicz A., Derkowski A. et al., Clays and Clay Minerals 2016 Vol. 64 P. 452-471
Experimental studies have shown that a sharp, high-frequency IR band at ~3615 cm(-1) (in H2O form) and at ~2685 cm(-1) (in D2O form) is a common feature for all smectites, and its position correlates with layer charge. In order to explain the molecular origin of this band in terms of total layer charge, charge localization, ...
Added: April 30, 2017
Стукалова О. В., Серова Н. С., Chepovskiy A. et al., Russian Electronic Journal of Radiology 2021 Т. 11 № 2 С. 32-45
В статье представлен обзор современной отечественной и зарубежной литературы, по-священной различным подходам к созданию моделей сердца, от первых очень простых компьютерных симуляций электрофизиологии до современных, основанных на магнитно-резонансной
томографии с контрастированием, с отражением не только анатомии, но и структуры миокар-да. Также в данном обзоре обсуждается вопрос практического применения данных технологий
для повышения эффективности сердечной ресинхронизирующей терапии, аблации ...
Added: August 8, 2021
Bari : Digilabs Pub., 2021
ASYS, the AIPEA School for Young Scientists. ASYS was successfully convened at the Andalusian Institute of
Earth Sciences (CSIC-UGR, Granada, Spain) on July 15 and 16, 2017, under the supervision of Dr. Claro Ignacio
Sainz Díaz, researcher of this centre, and in close connection to the 16th International Clay Conference in Granada
(ICC 2017). Young and not so-young ...
Added: September 5, 2021
Salikov R., Trainov K., Levina A. et al., Journal of Organic Chemistry 2017 Vol. 82 No. 1 P. 790-795
The rearrangement of cyclopropylketone arylhydrazones generated in situ from arylhydrazine hydrochlorides and ketones leads to formation of tryptamine derivatives. The use of (2-arylcyclopropyl)ethanones in the reactions with model 4-bromophenylhydrazine hydrochloride gives branched tryptamines with aryl groups in the α-position to the amino group, while (2-methylcyclopropyl)ethanone gives a mixture of α- and β-substituted products in a ratio of ...
Added: October 12, 2019
Nadezhdina E. Y., Rebrova O., Ivaschenko O. V. et al., Pituitary 2019 Vol. 22 No. 6 P. 574-580
Background Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier.
Aim To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD.
Methods Retrospective single-site comparative study included 349 ...
Added: October 23, 2019
Medvedev M., Kuznetsov N., Malishev V. et al., Mendeleev Communications 2019 Vol. 29 P. 190-193
Triallylborane-mediated thermal trans/cis-isomerization of α-allylated azaheterocycles is a unique stereoselective transformation providing straightforward access to important heterocycles. The main experimental features of this process, namely, thermodynamically controlled isomer ratio, 1,3-allylic strain as a driving force and regioselectivity are quantitatively described by quantum chemical calculations at B3LYP/6-31+G(d,p)/PCM(DMSO) level of theory. ...
Added: October 12, 2019
Loganathan N., Bowers G. M., Yazaydin A. O. et al., Journal of Physical Chemistry C 2018 Vol. 122 No. 41 P. 23460-23469
The intercalation of H2O, CO2, and other fluid species in expandable clay minerals (smectites) may play a significant role in controlling the behavior of these species in geological C-sequestration and enhanced petroleum production and has been the subject of intensive study in recent years. This paper reports the results of a computational study of the ...
Added: October 20, 2018
Svitanko I., Стройлов В. С., Новиков Ф. Н. et al., Russian Chemical Reviews 2020 Vol. 89 No. 8 P. 858-878
The review summarizes studies of chemical and biological processes occurring in human body
upon exposure to coronaviruses, in particular SARS-CoV-2. The mechanisms of viral particles
penetration into the cell and their replication, impact on the immune system and oxygen transport
systems are considered. The mechanisms of complications occurring as a consequence of viral
infection - vasculitis, thrombosis, cytokine storm ...
Added: May 19, 2020
Борисенко В. В., Веселова Т. Н., Терновой С. К. et al., Фундаментальная и прикладная математика 2020 Т. 23 № 2 С. 37-56
Рассматривается задача построения триангуляции внутренней поверхности аорты и
коронарных артерий. Это необходимо для создания гидродинамической модели крово-снабжения сердца. Исходными данными являются поперечные томографические срезы
сердца конкретного пациента толщиной0,5мм. Триангуляцию аорты и коронарных
артерий планируется использовать для расчёта кровотока в программном комплексе
FlowVision, предназначенном для моделирования трёхмерных течений жидкости и га-за. Результаты моделирования планируется применять в практической медицине для
диагностики ишемии ...
Added: August 16, 2021
Думлер А. А., Черепанов Ф. М., Терапия 2018 № 1(19) С. 109-118
This article is devoted to the methodological issues of the application of artificial intelligence techniques in preventive medicine. We showed a specific example of the neural network application allows not only to diagnose cardiovascular diseases, but also on a quantitative basis to predict their emergence and development in future periods of life. This allows you ...
Added: January 9, 2019