Improved Modeling of Peptide-Protein Binding Through Global Docking and Accelerated Molecular Dynamics Simulations

This work is licensed under a Creative Commons Attribution 4.0 International License.Peptides mediate up to 40% of known protein-protein interactions in higher eukaryotes and play a key role in cellular signaling, protein trafficking, immunology, and oncology. However, it is challenging to predict peptide-protein binding with conventional computational modeling approaches, due to slow dynamics and high peptide flexibility. Here, we present a prototype of the approach which combines global peptide docking using ClusPro PeptiDock and all-atom enhanced simulations using Gaussian accelerated molecular dynamics (GaMD). For three distinct model peptides, the lowest backbone root-mean-square deviations (RMSDs) of their bound conformations relative to X-ray structures obtained from PeptiDock were 3.3–4.8 Å, being medium quality predictions according to the Critical Assessment of PRediction of Interactions (CAPRI) criteria. GaMD simulations refined the peptide-protein complex structures with significantly reduced peptide backbone RMSDs of 0.6–2.7 Å, yielding two high quality (sub-angstrom) and one medium quality models. Furthermore, the GaMD simulations identified important low-energy conformational states and revealed the mechanism of peptide binding to the target proteins. Therefore, PeptiDock+GaMD is a promising approach for exploring peptide-protein interactions

Study of the impacts of droplets deposited from the gas core onto a gas-sheared liquid film

The results of an experimental study on droplet impactions in the flow of a gas-sheared liquid film are presented. In contrast to most similar studies, the impacting droplets were entrained from film surface by the gas stream. The measurements provide film thickness data, resolved in both longitudinal and transverse coordinates and in time together with the images of droplets above the interface and images of gas bubbles entrapped by liquid film. The parameters of impacting droplets were measured together with the local liquid film thickness. Two main scenarios of droplet-film interaction, based on type of film perturbation, are identified; the parameter identifying which scenario occurs is identified as the angle of impingement. At large angles an asymmetric crater appears on film surface; at shallow angles a long, narrow furrow appears. The most significant difference between the two scenarios is related to possible impact outcome: craters may lead to creation secondary droplets, whereas furrows are accompanied by entrapment of gas bubbles into the liquid film. In addition, occurrence of partial survival of impacting droplet is reported

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC00100

ЦИКЛОГРАММЫ ЗАПУСКА ХОЛЛОВСКОГО ДВИГАТЕЛЯ ST-25

The results of the start sequence diagram selection and experimental tests of the ST-25 Hall thruster intended for using on small spacecraft are presented. In order to reduce the mass and dimensions of the power processing unit of the propulsion system, it is proposed to exclude the hollow cathode keeper power supply from the structure of the power processing unit. The exclusion of the keeper power supply from the power processing unit made it necessary to select the thruster start sequence diagram. Four start sequence diagrams of the ST-25 Hall thruster start-up are considered: a) using a separate high voltage power supply for the hollow cathode keeper; b) using a separate low voltage power supply for the hollow cathode keeper; c) using a discharge power supply connected to the keeper through a high-resistance resistor to the hollow cathode keeper; d) connecting the keeper of the hollow cathode to the discharge power supply through an electronic switch with the possibility of adjusting the duration of the keeper connection to the discharge power supply. The graphs of changes in the thruster’s currents and voltages for various power supply circuits of the hollow cathode keeper are presented. The results of the choice of the start sequence diagram for the Hall engine ST-25 and the experimental studies carried out have shown that the use of an electronic switch with a steep pulse front makes it possible to obtain a reliable thruster start-up when a separate power supply for the keeper is excluded from the power processing unit of the propulsion system. As a result of the work carried out, it became possible to place the power processing unit for a propulsion system based on the ST-25 thruster in a volume of 2U. The possibility of using ST-25 thruster on spacecraft, the onboard electrical power of which is limited up to 200 W were confirmed.Наведено результати вибору циклограми запуску та експериментальних випробувань Холловського двигуна ST-25, призначеного для використання на малих космічних апаратах. З метою зниження маси та габаритів системи перетворення енергії двигунної установки зі структурної схеми системи перетворення енергії запропоновано виключити джерело електроживлення кіперу полого катоду. Виключення джерела електроживлення кіперу зі складу системи перетворення енергії викликало необхідність здійснити вибір циклограми запуску двигуна. Розглянуто чотири циклограми запуску Холловського двигуна ST-25: а) з використанням високовольтного джерела електроживлення кіперу полого катоду; б) з використанням низьковольтного джерела електроживлення кіперу полого катоду; в) з використанням для живлення кіперу полого катоду джерела живлення розряду, підключеного до кіперу через високоомний резистор; г) підключення кіперу полого катоду до джерела живлення розряду через електронний ключ з можливістю регулювання часу підключення кіперу до джерела розряду. Наведено графіки зміни струмів та напруг двигуна для різних схем електроживлення кіперу полого катоду. Результати вибору циклограми запуску Холловського двигуна ST-25 та проведені експериментальні дослідження показали, що використання електронного ключа з крутим фронтом імпульсу дозволяє забезпечити надійний запуск двигуна при виключенні зі складу системи перетворення енергії двигунної установки окремого джерела живлення кіперу. В результаті проведених досліджень виявилось можливим систему перетворення енергії для двигунної установки на базі двигуна ST-25 розмістити у об’ємі 2U. Підтверджено можливість використання двигунів ST-25 на космічних апаратах, бортова електрична потужність яких обмежена величиною 200 Вт.Приведены результаты выбора циклограммы запуска и экспериментальных испытаний Холловского двигателя ST-25, предназначенного для применения на малых космических аппаратах. С целью снижения массы и габаритов системы преобразования энергии двигательной установки из структуры системы преобразования энергии предложено исключить источник электропитания кипера полого катода. Исключение источника электропитания кипера из состава системы преобразования энергии вызвало необходимость осуществить выбор циклограммы запуска двигателя. Рассмотрены четыре циклограммы запуска Холловского двигателя ST-25: а) с использованием высоковольтного источника электропитания кипера полого катода; б) с использованием низковольтного источника электропитания кипера полого катода; в) с использованием для питания цепей кипера полого катода источника электропитания разряда, подключенного к киперу через высокоомный резистор; г) подключение кипера полого катода к источнику электропитания разряда через электронный ключ с возможностью регулирования длительности подключения кипера к источнику разряда. Приведены графики изменения токов и напряжений двигателя для предложенных схем электропитания кипера полого катода. Результаты выбора циклограммы запуска Холловского двигателя ST-25 и проведенные экспериментальные исследования показали, что применение электронного ключа с крутыми фронтами импульса позволило обеспечить надежный запуск двигателя при исключении из состава системы преобразования энергии двигательной установки отдельного источника электропитания кипера. В результате проведенных работ оказалось возможным систему преобразования энергии для двигательной установки на базе двигателя ST-25 разместить в объеме 2U. Подтверждена возможность применения двигателей ST-25 на космических аппаратах, бортовая электрическая мощность которых ограничена величиной 200 Вт

Three-dimensional investigation of liquid film structure at the initial area of annular-dispersed flow

Initial stage of downward flow of gas-sheared liquid film in a vertical rectangular duct was studied using brightness-based laser-induced fluorescence technique. Measurements were resolved along both longitudinal and transverse coordinates and time. The initial high-frequency waves which are formed at the inlet were found to be two-dimensional. These waves are promptly broken into localised horseshoe-shaped waves which merge downstream to form large-scale quasi-2D disturbance waves. Peculiarities of three-dimensional evolution of waves of different types were studied in a wide range of flow parameters

Three-dimensional investigation of liquid film structure at the initial area of annular-dispersed flow

Initial stage of downward flow of gas-sheared liquid film in a vertical rectangular duct was studied using brightness-based laser-induced fluorescence technique. Measurements were resolved along both longitudinal and transverse coordinates and time. The initial high-frequency waves which are formed at the inlet were found to be two-dimensional. These waves are promptly broken into localised horseshoe-shaped waves which merge downstream to form large-scale quasi-2D disturbance waves. Peculiarities of three-dimensional evolution of waves of different types were studied in a wide range of flow parameters

UAV-Derived Data Application for Environmental Monitoring of the Coastal Area of Lake Sevan, Armenia with a Changing Water Level

The paper presents the range and applications of thematic tasks for ultra-high spatial resolution data from small unmanned aerial vehicles (UAVs) in the integral system of environmental multi-platform and multi-scaled monitoring of Lake Sevan, which is one of the greatest freshwater lakes in Eurasia. From the 1930s, it had been subjected to human-driven changing of the water level with associated and currently exacerbated environmental issues. We elaborated the specific techniques of optical and thermal surveys for the different coastal sites and phenomena in study. UAV-derived optical imagery and thermal stream were processed by a Structure-from-Motion algorithm to create digital surface models (DSMs) and ortho-imagery for several key sites. UAV imagery were used as additional sources of detailed spatial data under large-scale mapping of current land-use and point sources of water pollution in the coastal zone, and a main data source on environmental violations, especially sewage discharge or illegal landfills. The revealed present-day coastal types were mapped at a large scale, and the net changes of shoreline position and rates of shore erosion were calculated on multi-temporal UAV data using modified Hausdorff’s distance. Based on highly-detailed DSMs, we revealed the areas and objects at risk of flooding under the projected water level rise to 1903.5 m along the west coasts of Minor Sevan being the most popular recreational area. We indicated that the structural and environmental state of marsh coasts and coastal wetlands as potential sources of lake eutrophication and associated algal blooms could be more efficiently studied under thermal UAV surveys than optical ones. We proposed to consider UAV surveys as a necessary intermediary between ground data and satellite imagery with different spatial resolutions for the complex environmental monitoring of the coastal area and water body of Lake Sevan as a whole

Experimental study of air delivery into water-conveyance system of the radial-axial turbine

The paper presents an experimental study of oscillatory response in the Francis turbine of hydraulic unit. The experiment was performed on large-scale hydrodynamic test-bench with impeller diameter of 0.3 m. The effect of air injection on the intensity of pressure pulsations was studied at the maximum pressure pulsations in the hydraulic unit. It was revealed that air delivery into the water-conveyance system of the turbine results in almost two-fold reduction of pressure pulsations