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Martini 3, the latest version of the widely used Martini force field for coarse-grained molecular dynamics simulations, is a promising tool to investigate proteins in phospholipid bilayers. However, simulating other lipid environments, such as detergent micelles, presents challenges due to the absence of validated parameters for their constituent molecules. Here, we propose parameters for the micelle-forming surfactant, dodecylphosphocholine (DPC). These result in micelle assembly with aggregation numbers in agreement with experimental values. However, we identified a lack of hydrophobic interactions between transmembrane helix protein dimers and the tails of DPC molecules, preventing insertion and stabilization of the protein in the micelles. This problem was also observed for protein insertion by self-assembling 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or dipalmitoylphosphatidylcholine (DPPC) bilayers. We propose the reduction of the non-bonded interactions between protein and water beads by 10% as a simple and effective solution to this problem that enables protein encapsulation in phospholipid micelles and bilayers without altering protein dimerization or bilayer structure.Abstract Figure

SUMMARYNeural stem cell (NSC) proliferation and differentiation in the mammalian brain decreases to minimal levels postnatally. Nevertheless, neurogenic niches persist in the adult cortex and hippocampus in rodents, primates and humans, with adult NSC differentiation sharing key regulatory mechanisms with development. Adult neurogenesis impairments have been linked to Alzheimer’s Disease (AD) pathology. Addressing these impairments is a promising new avenue for therapeutic intervention based on neurogenesis. However, this possibility has been hindered by technical difficulties of using in-vivo models to conduct screens, including working with scarce NSCs in the adult brain and differences between human and mouse models or ethical limitations. In our study, we use a combination of mouse and human stem cell models to circumvent these issues and perform comprehensive characterization of a novel neurogenic compound usingin vitroscreening. Our work focuses on the brain-derived neurotrophic factor (BDNF) pathway, a pivotal neurotrophin in the regulation of neuronal growth and differentiation via its receptor tyrosine receptor kinase B (TrkB). We describe the design, chemical synthesis and biological characterization of ENT-A011, a steroidal dehydroepiandrosterone (DHEA) derivative and BDNF mimetic with neuroprotective and neurogenic actions. The compound is able to increase proliferation of mouse primary adult hippocampal NSCs and embryonic cortical NSCs, in the absence of EGF/FGF, while reducing Amyloid-β (Aβ) induced cell death, acting specifically through TrkB activation. The compound is also able to increase astrocytic gene markers involved in NSC maintenance, protect hippocampal neurons from Αβ toxicity and prevent synapse loss after Aβ treatment. To provide a translational link to human cells, we also used neural progenitor cells (NPCs) differentiated from three human induced pluripotent stem cell lines from healthy and AD donors. Our findings suggest that ENT-A011 successfully induces proliferation and prevents cell death after Aβ toxicity of human NPCs. Additionally, using RNAseq profiling, we demonstrate that the compound acts through a core gene network shared with BDNF. Our work characterizes a novel synthetic BDNF mimetic with potential neurogenic and neuroprotective actions in Alzheimer’s disease via stem cell-based screening, demonstrating the promise of stem cell systems for short-listing competitive candidates for further testing.

Relative binding free energy calculations in drug design are becoming a useful tool in facilitating lead binding affinity optimization in a cost- and time-efficient manner. However, they have been limited by technical challenges such as the manual creation of large numbers of input files to set up, run, and analyze free energy simulations. In this Application Note, we describe FEPrepare, a novel web-based tool, which automates the setup procedure for relative binding FEP calculations for the dual-topology scheme of NAMD, one of the major MD engines, using OPLS-AA force field topology and parameter files. FEPrepare provides the user with all necessary files needed to run a FEP/MD simulation with NAMD. FEPrepare can be accessed and used at https://feprepare.vi-seem.eu/.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of a community effort, the “Billion molecules against Covid-19 challenge”, to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 potentially active molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (Nsp12 domain), and (alpha) spike protein S. Overall, 27 potential inhibitors were experimentally confirmed by binding-, cleavage-, and/or viral suppression assays and are presented here. All results are freely available and can be taken further downstream without IP restrictions. Overall, we show the effectiveness of computational techniques, community efforts, and communication across research fields (i.e., protein expression and crystallography, in silico modeling, synthesis and biological assays) to accelerate the early phases of drug discovery.

In this paper the control scheme of a three-level three-phase inverter for grid integration of distributed generation (DG) units is investigated. Furthermore, the inverter compensates the reactive power of the load. The presented control scheme is based on instantaneous power theory in order to generate the appropriate inverter reference currents. In the outer DC bus voltage control loop and in the inner current control loop, the fuzzy logic (FL) control and the Proportional-Resonant (PR) control is applied respectively. The switching pattern generation is achieved using Space Vector Pulse Width Modulation technique. The steady state and dynamic response of the proposed electric power system has been evaluated under various operating conditions. Simulation results verify the effectiveness of the proposed control system.

In this paper a grid connected photovoltaic (PV) system is presented. The grid integration of the PV system is carried out via a three phase three level neutral point clamped (NPC) inverter. To control the inverter a modified version of voltage oriented control (VOC) method and the space vector pulse width modulation (SVPWM) technique have been applied. With the proposed modification the PV system operates as a shunt active power filter (SAPF), a reactive power compensator, and a load’s current balancer simultaneously. In this way the PV system operates more efficiently compared to the conventional PV systems and offers ancillary services to electric power system. The effectiveness of the proposed control scheme is established through simulation results with Matlab/Simulink in steady state and transient response of the electric power distribution system.

In this paper is analyzed and simulated on the computer the operation of a three level H-bridge converter as well as its parallel operations. Based on the simulation results the operating behavior between a) a three level H-bridge neutral point clamped converter, b) a three level H-bridge neutral point clamped converter with parallel elements and c) two three level H-bridge neutral point clamped converters parallel connected is being compared. From the simulation results is obvious that in the first two cases the ripples, the distortion in primary and secondary winding currents, and the power factor are quite satisfactory and almost identical to each other. In the third case as compared with the first two, we observe that current harmonics with higher amplitude appear in the primary winding of the transformer.

In this paper, a photovoltaic (PV) system, with maximum power point tracking (MPPT), connected to a three phase grid is presented. The connection of photovoltaic system on the grid takes place in one stage using voltage source inverter (VSI). For a better utilization of the photovoltaic system, the control strategy applied is based on p–q theory. According to this strategy during sunlight the system sends active power to the grid and at the same time compensates the reactive power of the load. In case there is no sunlight (during the night for instance), the inverter only compensates the reactive power of the load. In this paper the use of p–q theory to supply the grid with active power and compensate the reactive power of the load is investigated. The advantage of this control strategy is that the photovoltaic system is operated the whole day. Furthermore, the p–q theory uses simple algebraic calculations without demanding the use of PLL to synchronize the inverter with the grid.

In this paper, a photovoltaic (P/V) system, with maximum power point tracking (MPPT), connected to a three phase grid is presented. The connection of photovoltaic system on the grid takes place in one stage using voltage source inverter (VSI). For a better utilization of the photovoltaic system, the control strategy applied is based on p-q theory. According to this strategy during sunlight the system sends active power to the grid and at the same time compensates the reactive power of the load. In case there is no sunlight (during the night for instance), the inverter only compensates the reactive power of the load. The advantage of this strategy is the operation of the photovoltaic system the whole day. In this paper the p-q theory is proposed, which does not demand the use of PLL and introduces simple algebraic calculations.

In this paper the impact of photovoltaic (PV) system connected to the medium voltage distribution grid using three-phase three-level inverter and step-up transformer will be investigated. The PV inverter is capable to control active and reactive power independently. The impact to the grid voltage profile of both active and reactive power regulation of the PV system will be examined. In order to simplify the control scheme and improve the performance of the converters the p-q theory has been chosen due to the ability to compensate the reactive power of the load. The proposed electric power system was investigated via simulation results during steady state and transient response. The analysis will be focused on the grid voltage profile improvement regarding of the of the inverter's active and reactive power injection.

© 2012 Tsengenes and Adamidis, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Performance Evaluation of PI and Fuzzy Controlled Power Electronic Inverters for Power Quality Improvement

This paper presents a shunt active filter which eliminates current harmonics and compensates the reactive power of the load. The majority of shunt active power filter control methods which have been presented require a complex and sophisticated mathematical model, especially for the tuning of the PI controllers. To simplify and improve the shunt active filter control system, fuzzy logic theory is applied. In this paper, by the way of controlling the capacitor voltage of the dc bus a fuzzy logic algorithm is implemented. One such algorithm is also implemented to control the output current of the inverter. The performance of the capacitor voltage fuzzy logic control system was investigated, and the improvement of the dynamic response of the fuzzy controller compared to the conventional PI controller became evident. For the reduction of the grid current THDi index, a fuzzy logic hysteresis current controller is investigated. In order to improve the performance of shunt active filter under non ideal grid voltages, a modified version of the p-q theory is proposed. The simulation results are presented and discussed showing the advantages of fuzzy logic theory in the dc bus voltage control and current control.

In this paper the connection in single stage single phase of a photovoltaic system (PV) to the electric power system is presented. A modified version of p-q theory is proposed in order to implement this strategy in a single phase inverter. To extract maximum power from the PV array an algorithm Maximum Power Point Tracking (MPPT) is used. For the switching pattern generation the hysteresis controller is used. The behavior of both the permanent and the transient state, which includes changing the radiation and the load is analyzed using a computer.

This paper investigates the operation of a Distributed Generation (DG) unit which is connected via a three-phase voltage-source inverter to the distribution grid. The current control method with Space Vector pulse width modulation (SVPWM) is examined and compared to other current control methods. The strategy, which has been developed to control the reactive power and have a better utilization of DG unit, uses the p-q theory to achieve uninterrupted compensation of the reactive power of the system. A PI controller is used to control the active power and regulate the voltage of the capacitor. Finally, the proposed electrical power system is simulated on the computer and the steady-state and dynamic response of the system is evaluated.

In this paper the problems created by non linear load as well as the solutions having been applied so far are briefly reviewed. A new simple and effective reference current generation method of a shunt active power filter (SAPF) is proposed. This method aims at eliminating harmonics from the mains currents. It also compensates the reactive power which is created from the linear and non linear loads. The new method is applied both in the case that mains voltages are ideal and in the case that mains voltages are non ideal. The new method is compared to the conventional p-q theory and the results are analyzed and commented on. From the analysis and the commentary the advantages of the new technique are concluded.

This paper initially refers to the devices used to compensate upper harmonics. Subsequently, it examines the principal methods for controlling an active filter which is connected to the electricity grid in order to compensate reactive power and to eliminate the electricity harmonics. The mathematic model following the p-q theory is analyzed for the creation of a reference current, aiming at the elimination of the upper harmonics and at reactive power compensation. An improved control method is presented regarding current control through the use of a Hysteresis Band with an altering tolerance band. In this way, current control is adjusted onto the load current.