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The 90-kDa heat shock protein (Hsp90) is a homodimeric molecular chaperone with ATPase activity, which has become an intensely studied target for the development of drugs for the treatment of cancer, neurodegenerative and infectious diseases. The equilibrium between Hsp90 dimers and oligomers is important for modulating its function. In the absence of ATP, the passive chaperone activity of Hsp90 dimers and oligomers has been shown to stabilize client proteins as a holdase, which enhances substrate binding and prevents irreversible aggregation and precipitation of the substrate proteins. In the presence of ATP and its associated cochaperones, Hsp90 homodimers act as foldases with the binding and hydrolysis of ATP driving conformational changes that mediate client folding. Crystal structures of both wild type and W320A mutant Hsp90αMC (middle/C-terminal domain) have been determined, which displayed a preference for hexameric and dimeric states, respectively. Structural analysis showed that W320 is a key residue for Hsp90 oligomerization by forming intermolecular interactions at the Hsp90 hexameric interface through cation-π interactions with R367. W320A substitution results in the formation of a more open conformation of Hsp90, which has not previously been reported, and the induction of a conformational change in the catalytic loop. The structures provide new insights into the mechanism by which W320 functions as a key switch for conformational changes in Hsp90 self-oligomerization, and binding cochaperones and client proteins.Communicated by Ramaswamy H. Sarma.

The heat shock protein 90 (Hsp90) family of molecular chaperones mediates the folding and activation of client proteins associated with all 10 hallmarks of cancer. Herein, the design, synthesis, and biological validation of Hsp90α-selective inhibitors that contain a tertiary alcohol are reported. Forty-one analogues were synthesized to modulate hydrogen-bonding interactions and to probe for steric and hydrophobic interactions within the Hsp90α binding site. Cocrystal structures of lead compound

The 90 kDa heat-shock protein (Hsp90) is an abundant molecular chaperone that is essential to activate, stabilize and regulate the function of a plethora of client proteins. As drug targets for the treatment of cancer and neurodegenerative diseases, Hsp90 inhibitors that bind to the N-terminal ATP-binding site of Hsp90 have shown disappointing efficacy in clinical trials. Thus, allosteric regulation of the function of Hsp90 by compounds that interact with its middle and C-terminal (MC) domains is now being pursued as a mechanism to inhibit the ATPase activity and client protein-binding activity of Hsp90 without concomitant induction of the heat-shock response. Here, the crystal structure of the Hsp90αMC protein covalently linked to a coumarin derivative, MDCC {7-diethylamino-3-[N-(2-maleimidoethyl)carbamoyl]coumarin}, which is located in a hydrophobic pocket that is formed at the Hsp90αMC hexamer interface, is reported. MDCC binding leads to the hexamerization of Hsp90, and the stabilization and conformational changes of three loops that are critical for its function. A fluorescence competition assay demonstrated that other characterized coumarin and isoflavone-containing Hsp90 inhibitors compete with MDCC binding, suggesting that they could bind at a common site or that they might allosterically alter the structure of the MDCC binding site. This study provides insights into the mechanism by which the coumarin class of allosteric inhibitors potentially disrupt the function of Hsp90 by regulating its oligomerization and the burial of interaction sites involved in the ATP-dependent folding of Hsp90 clients. The hydrophobic binding pocket characterized here will provide new structural information for future drug design.

We study a cost effective and easy way to fabricate stable, uniform and large area surface-enhanced Raman scattering (SERS) substrates. The AgNPs with varying diameters have been fabricated through a thermally treating method on SiO2/Si substrate which present a high sensitivity, good uniformity and good stability. By using rhodamine 6G (R6G) molecule as analyte, the maximized detection limit is as low as 10−8 M. The deviation of SERS intensity by using proposed AgNPs SERS substrate is less than 15% which indicates its good uniformity. This work provides an efficiently way of fabricating industry SERS substrates which are good candidate in practical application in medicine, food safety and biotechnology.

Significance SAMD9 and SAMD9L (SAMD9/9L) are important innate immune defenders against viruses and the development of myeloid tumors. They form a crucial host barrier that poxviruses must overcome for successful infection. A myriad of human diseases including many pediatric myelodysplastic syndromes are caused by mutations in SAMD9/9L. However, the molecular functions of SAMD9/9L and how their functions are executed are unknown, hindering progress in developing effective therapies for SAMD9/9L-associated human diseases. Here, we identified the structure and function of a SAMD9/9L effector domain that is essential for their physiological functions as well as the pathogenic effects exerted by patient-derived mutations. Our study revealed a potential therapeutic target for SAMD9/9L-associated human diseases., SAMD9 and SAMD9L (SAMD9/9L) are antiviral factors and tumor suppressors, playing a critical role in innate immune defense against poxviruses and the development of myeloid tumors. SAMD9/9L mutations with a gain-of-function (GoF) in inhibiting cell growth cause multisystem developmental disorders including many pediatric myelodysplastic syndromes. Predicted to be multidomain proteins with an architecture like that of the NOD-like receptors, SAMD9/9L molecular functions and domain structures are largely unknown. Here, we identified a SAMD9/9L effector domain that functions by binding to double-stranded nucleic acids (dsNA) and determined the crystal structure of the domain in complex with DNA. Aided with precise mutations that differentially perturb dsNA binding, we demonstrated that the antiviral and antiproliferative functions of the wild-type and GoF SAMD9/9L variants rely on dsNA binding by the effector domain. Furthermore, we showed that GoF variants inhibit global protein synthesis, reduce translation elongation, and induce proteotoxic stress response, which all require dsNA binding by the effector domain. The identification of the structure and function of a SAMD9/9L effector domain provides a therapeutic target for SAMD9/9L-associated human diseases.

The optimal energy management of a hybrid powertrain has the task to provide the required traction power combining both power sources in the best way. This can be achieved well if the future drive cycle is known/precomputed. However, both speed and traction power requirement may deviate from the expected ones due to many factors, like traffic, weather etc. Against this background, it might be sensible to recompute them whenever needed to keep using the latest future information. Unfortunately, this computation is typically too slow for real time use. In this paper we propose a control structure in which the real time task is solved by a predictive controller which tracks the optimal reference from the cloud, and requests an update of the reference regularly. The update can integrate new information from V2X. This asynchronous operation allows recovering most of the performance of the perfect prediction, while removing tight constraints on the offline computation and copes better with interruptions in communications to the cloud.

Knowledge of the upcoming traffic velocity along a route can help in many respects, among them optimizing energy management for hybrid vehicles, which, for instance, could reduce instantaneous battery usage if a traffic jam is upcoming in the next future. While such kind of knowledge can hardly be precise on a single-vehicle level, we show in this paper that a prediction method which combines present and past Vehicle-to-Everything (V2X) information can strongly improve the energy efficiency. Our approach is first compared with other prevailing prediction methods and its advantages in terms of stability and accuracy are shown. Then the prediction results are applied in a hybrid powertrain control example, in which its potential in fuel savings are illustrated.

A priori information about the future traffic conditions along the planned route can be essential for optimal hybrid powertrain energy management. However, due to the limited sensor range of a single vehicle, it cannot be acquired locally. In recent time, V2X (decentralized wireless vehicle to everything) has been receiving much attention as a way to obtain and share information from different distributed sources. V2X data can provide updated information on traffic at different locations. Still, this information will be obsolete when the corresponding positions are reached due to changing traffic, and an optimal strategy based on outdated information may not bring the full benefit. Against this background, we propose a method based on a velocity prediction approach which utilizes V2X data currently available in the market in combination with historical data, to obtain a prediction of the expected traffic conditions at in the close future. Actual measurements on a city highway in Linz, Austria, are used to estimate the potential of the approach. Even for rather mild changes in traffic conditions, a reduction of up to 4% in terms fuel consumption over this track was found, confirming the potential benefit of this method.

Existing mechanical HVDC circuit breakers (CB) are capable of interrupting HVDC currents within several tens of milliseconds, but this is too slow to satisfy the requirements of a reliable HVDC grid. HVDC CB based on semiconductors can easily overcome the limitations of operating speed, but need large number of the series (parallel) connection of electronic switching devices. To overcome these shortcomings, this paper introduces a topology of hybrid CB; this paper first describes the principle of hybrid CB; then a control strategy of fault pre-treatment is also proposed, that is, the ‘pre-action and action (or recovery)’ of the switches, in order to improve the breaking speed of the hybrid CB and the equalising circuit of its solid-state switch has been designed. The proposed topology and control strategy do not produce loss in the normal operation of CB, and instantaneous trigger solid-state switch with quickly cutting short-circuit current during short-circuit faults; at last the simulation and experiment of the hybrid HVDC CB have also been done. The results turn out when a short circuit occurs, the hybrid HVDC CB can quickly break the short-circuit current; the buffer circuit can be provided for the release of the stored energy circuit.

The STENOFOLIA homeodomain binds promoter DNA as a tetramer and the α3 helix binds DNA in both the major and minor grooves., Homeobox transcription factors are key regulators of morphogenesis and development in both animals and plants. In plants, the WUSCHEL-related homeobox (WOX) family of transcription factors function as central organizers of several developmental programs ranging from embryo patterning to meristematic stem-cell maintenance through transcriptional activation and repression mechanisms. The Medicago truncatula STENOFOLIA (STF) gene is a master regulator of leaf-blade lateral development. Here, the crystal structure of the homeodomain (HD) of STF (STF-HD) in complex with its promoter DNA is reported at 2.1 Å resolution. STF-HD binds DNA as a tetramer, enclosing nearly the entire bound DNA surface. The STF-HD tetramer is partially stabilized by docking of the C-terminal tail of one protomer onto a conserved hydrophobic surface on the head of another protomer in a head-to-tail manner. STF-HD specifically binds TGA motifs, although the promoter sequence also contains TAAT motifs. Helix α3 not only serves a canonical role as a base reader in the major groove, but also provides DNA binding in the minor groove through basic residues located at its C-terminus. The structural and functional data in planta reported here provide new insights into the DNA-binding mechanisms of plant-specific HDs from the WOX family of transcription factors.

Using knowledge of the future route and its topology is known to offer substantial fuel savings, and this is even more true for hybrid electric vehicles, as the battery use can be planned in advance, for instance to take into account coming slopes. However, traffic or other environmental conditions can force to deviate from the initial planning making it no longer optimal.In this paper, we propose a flexible double layer approach for energy management of hybrid vehicles able to cope with traffic changes. First, before departure, an expected optimal speed and powertrain state reference is computed on a cloud and sent to an on-board controller. Simple, route-specific engine on/off rules are extracted by the controller and used for an on-board fast convex optimization, which can be conducted frequently along the drive, adapting the references to take into account changes of traffic conditions over longer sections of the route as communicated by V2X. Abrupt disturbances are handled by a lower level Model Predictive Control (MPC). If the condition changes are very substantial, so that the empirical on/off rule seems questionable, the cloud can be asked to perform a full optimization again.

In this project we design and study a differential phase surface plasmon resonance sensor combining with microfluidic technology. The differential phase Surface Plasmon Resonance (SPR) sensor is constructed by applying the Kretschman plasmon excitation structure and combing with interference spectroscopy. Through making use of simulation and experimental method, the principle of SPR sensor is theoretically and experimentally studied. In this project, we apply the SPR sensor in testing urea solution with varying weight concentration. Through the results, it can be observed that the plasma resonance absorption ranges from 640 nm to 840 nm and its detection limits can reach 0.0004 RIU. Due to its tunable plasma absorption and lower detection limits, the microfluidic differential phase surface plasmon resonance sensor illustrates a promising future in chemistry, physics and biology.

Programmed cell death (PCD) and apoptosis have key functions in development and disease resistance in diverse organisms; however, the induction of necrosis remains poorly understood. Here, we identified a semi-dominant mutant allele that causes the necrotic death of the entire seedling (DES) of wheat (Triticum aestivum L.) in the absence of any pathogen or external stimulus. Positional cloning of the lethal allele mDES1 revealed that this premature death via necrosis was caused by a point mutation from Asp to Asn at amino acid 441 in a nucleotide-binding leucine-rich repeat protein containing nucleotide-binding domain and leucine-rich repeats. The overexpression of mDES1 triggered necrosis and PCD in transgenic plants. However, transgenic wheat harboring truncated wild-type DES1 proteins produced through gene editing that exhibited no significant developmental defects. The point mutation in mDES1 did not cause changes in this protein in the oligomeric state, but mDES1 failed to interact with replication protein A leading to abnormal mitotic cell division. DES1 is an ortholog of Sr35, which recognizes a Puccinia graminis f. sp. tritici stem rust disease effector in wheat, but mDES1 gained function as a direct inducer of plant death. These findings shed light on the intersection of necrosis, apoptosis, and autoimmunity in plants.

The task of energy management for hybrid electric vehicles (HEV) consists in providing the requested traction power by splitting the demand between electrical and mechanical energy sources. The best performance can be achieved if the power split can be computed over the whole trip at once, e.g. using Dynamic Programming (DP). However, actual travel conditions are prone to change with respect to the assumed ones, so that updates are needed. Recomputing the optimal power split for the whole remaining route via DP is hardly feasible due to the actual travel conditions, so approximate solutions are needed. In this paper, we propose an online-capable strategy for a parallel HEV based on the minimization of total losses and heuristics for engine on/off and gear actions. It yields a very good approximation of the DP solution with little computational burden.

Homeobox transcription factors are key regulators of morphogenesis and development in both animals and plants1. In plants, the WUSCHEL-related homeobox (WOX) family transcription factors function as central organizers of several developmental programs from embryo patterning to meristematic stem cell maintenance through transcriptional activation and repression2-4. The structure of WOX Homeodomain (HD) and the molecular mechanism of its interaction with DNA are unknown. Here, we report the 2.1 Å crystal structure of the STENOFOLIA (STF) HD fromMedicago truncatulain complex with DNA. STF binds DNA as a novel cooperative tetramer, enclosing nearly entire bound DNA surface. The STF tetramer is partially stabilized by docking of the C-terminal tail from one protomer onto a conserved hydrophobic surface on the head of another in a head-to-tail manner. Helix α3 not only serves a canonical role as a base reader in the major groove, but also provides extensive binding to DNA in the minor groove. Our structural and functional data reveal that STF specifically targets ‘TGA’ sequence and the cooperative tetrameric binding with DNA is key to transcriptional repression in plants. Our data reveal an unprecedented HD:DNA recognition mechanism, representing the first plant HD structure from WOX family of transcription factors.

Eco-driving is a way to improve performance — mainly energy consumption — of road vehicles by computing an optimal speed and gear shifting profile based on vehicle data and road profile, e.g. slopes or speed limits. It mainly focuses on long haul scenarios such as highways, considering longitudinal movement only. Lateral acceleration of a vehicle is a critical quantity both in terms of comfort and safety, but its impact on fuel consumption or emissions is rarely considered or believed to be limited [1], as it does not affect directly the operating point of the engine. However, on country roads which usually present much stronger curvatures, lateral acceleration may be a critical constraint. In this paper, the impact of lateral acceleration limits on optimal solutions to multi-objective eco-driving is investigated. It is found that it may play an even more critical role than longitudinal acceleration with respect to fuel consumption and NOx emission. As a consequence, the choice of limits to lateral acceleration on curvy roads should be set very carefully in order to achieve a balance between energy saving, drivers comfort and travel time. The results of this work are validated on a high-feasibility Hardware-in-the-loop (HIL) system calibrated with data from Real Driving Emissions tests.

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 protein folding machinery results in a combinatorial attack on numerous oncogenic pathways. Seventeen small-molecule inhibitors of Hsp90 have entered clinical trials, all of which bind the Hsp90 N-terminus and exhibit pan-inhibitory activity against all four Hsp90 isoforms. pan-Inhibition of Hsp90 appears to be detrimental as toxicities have been reported alongside induction of the pro-survival heat shock response. The development of Hsp90 isoform-selective inhibitors represents an alternative approach towards the treatment of cancer that may limit some of the detriments. Described herein is a structure-based approach to design isoform-selective inhibitors of Hsp90β, which induces the degradation of select Hsp90 clients without concomitant induction of Hsp90 levels. Together, these initial studies support the development of Hsp90β-selective inhibitors as a method to overcome the detriments associated with pan-inhibition., The molecular chaperone Hsp90 oversees the folding of many proteins associated with cancer progression but existing small-molecule inhibitors of this pathway are not isoform-selective. Here, the authors rationally design an Hsp90 inhibitor that displays high selectivity for the Hsp90β isoform.

Interleukin-18 (IL-18) is a pleiotropic pro-inflammatory cytokine belonging to the IL-1 superfamily. IL-18 plays an important role in host innate and adaptive immune defense but its aberrant activities are also associated with inflammatory diseases such as rheumatoid arthritis and Crohn's disease. IL-18 activity is modulated in vivo by its naturally occurring antagonist, IL-18 Binding Protein (IL-18BP). Recent crystal structures of human IL-18 (hIL-18) in complex with its antagonists or cognate receptor(s) have revealed a conserved binding interface on hIL-18. Through virtual screening of the National Cancer Institute Diversity Set II and in vitro competitive ELISA we have identified three compounds (NSC201631, NSC80734, and NSC61610) that disrupt hIL-18 binding to the ectromelia virus IL-18BP. Through cell-based bioassay, we show that NSC80734 inhibits IL-18-induced production of IFN-γ in a dose-dependent manner with an EC50 of ~250 nM. Our results and methodology presented here demonstrate the feasibility of developing small molecule inhibitors that specifically target the rather large interface of IL-18 that is involved in extensive protein-protein interactions with both IL-18BP and its cognate receptor(s). Our data therefore provide the basis for an approach by which small molecules can be identified that modulate IL-18 activity.

Entrances into highway represent critical sections, as entering vehicles are bound to merge with the existing traffic at a fixed junction point almost independently from the traffic conditions-in some sense a “constrained” cut-in manoeuver. Advanced driver-assistance systems (ADAS) need to perform correctly under these conditions as well, but could also be used to facilitate merging and reducing risks. In particular, vehicles on the main road could adapt their speeds-or even change lane-provided an estimate of the entering vehicle's time to merge is available, exactly as a human driver would do. This paper is concerned with providing such an estimate. To this end, we observe that the speed profile on the entering ramps is rather well predictable if the acceleration of the entering vehicles is described as a function of their actual distance from the junction point. Still, uncertainties remain and to cope with them, we use a stochastic prediction model based on Dynamic Bayesian Network. The result are probability distribution functions of the time to merge based on the observation of speed and distance of the entering vehicle once they become visible to the traffic on the main road. Experimental data are used to illustrate the model structure and the parameter determination. The model quality is then assessed by comparing statistics from simulations with the one recorded on road. The possible use of the model as a tool for traffic prediction algorithm embedded in ADAS and an extension to existing highway stochastic traffic models are shortly discussed at the end of the paper.

A novel static synchronous compensator (STATCOM) based on hybrid cascaded multi-level converter (HCMC) is presented in this study, i.e HCMC-STATCOM, which combines the advantages of the traditional two-level converter and cascaded H-bridge converter. However, the topology and control system are relatively complex. It is difficult to coordinate the two key parts in steady operation. This study firstly introduces topology and working principle of the HCMC-STATCOM. Moreover then, the DC voltage of the two-level converter and the number of H-bridge sub-modules in WSC are optimised. In order to achieve the coordinated control of two key parts, a control strategy is proposed to achieve the coordination and synchronisation between the two parts of the HCMC-STATCOM. Finally the 35 kV/ ± 100 Mvar HCMC-STATCOM simulation model is built by using power systems computer aided design/electromagnetic transients including DC (PSCAD/EMTDC), the results show that the effectiveness of the coordinated control strategy and the accuracy of the theoretical analysis.

A rapid optical microarray imaging approach for anticancer drug screening at specific cancer protein-protein interface targets with binding kinetics and validation by a mass sensor is reported for the first time. Surface plasmon resonance imager (SPRi) demonstrated a 3.5-fold greater specificity for interactions between murine double minute 2 protein (MDM2) and wild-type p53 over a nonspecific p53 mutant in a real-time microfluidic analysis. Significant percentage reflectivity changes (Δ%R) in the SPRi signals and molecular-level mass changes were detected for both the MDM2-p53 interaction and its inhibition by a small-molecule Nutlin-3 drug analogue known for its anticancer property. We additionally demonstrate that synthetic, inexpensive binding domains of interacting cancer proteins are sufficient to screen anticancer drugs by an array-based SPRi technique with excellent specificity and sensitivity. This imaging array, combined with a mass sensor, can be used to study quantitatively any protein-protein interaction and screen for small molecules with binding and potency evaluations.

Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

Cellular membranes are maintained as closed compartments, broken up only transiently during membrane reorganization or lipid transportation. However, open-ended membranes, likely derived from scissions of the endoplasmic reticulum, persist in vaccinia virus-infected cells during the assembly of the viral envelope. A group of viral membrane assembly proteins (VMAPs) were identified as essential for this process. To understand the mechanism of VMAPs, we determined the 2.2-A crystal structure of the largest member, named A6, which is a soluble protein with two distinct domains. The structure of A6 displays a novel protein fold composed mainly of alpha helices. The larger C-terminal domain forms a unique cage that encloses multiple glycerophospholipids with a lipid bilayer-like configuration. The smaller N-terminal domain does not bind lipid but negatively affects lipid binding by A6. Mutations of key hydrophobic residues lining the lipid-binding cage disrupt lipid binding and abolish viral replication. Our results reveal a protein modality for enclosing the lipid bilayer and provide molecular insight into a viral machinery involved in generating and/or stabilizing open-ended membranes.

DC distribution network topology includes: chain structure, two-terminal structure and ring structure. This paper firstly introduces a device of Flexible Alternative Current Transmission System: static synchronous series compensator with fault current limiting. DC distribution network with SSSC-FCL can develop the power quality of distribution network and improve the stability. When the fault occurs, the SSSC-FCL can effectively limit the short circuit current to ensure the safety of system. And then this paper also introduces the main advantages of the DC distribution network and the topology, basic control methods of SSSC-FCL. Finally put forward a DC distribution network topology structure with SSSC-FCL. With the use of PSCAD/EMTDC to model and simulate the DC distribution network, the result of the simulation verified the feasibility and effectiveness of the DC network topology structure with SSSC-FCL.

In the new economic situation, more and more researchers began to pay attention to the electricity market. Government departments attach great importance to the growth of electricity consumption. This paper tries to investigate the relationship between electricity consumption and economic growth in Fujian Province China, using monthly data during January 2014 (2014m01) to May 2017 (2017m05). Investment, consumption and export data instead of only Gross Domestic Product (GDP) data is used to represent the economic growth, which indicates their individual effect on electricity consumption. Dickey-Fuller (DF) tests reveal that all the time series are non-stationary and individually integrated of order one. Long-run cointegration relationships between investment, consumption, export and electricity consumption individually are revealed by Engel-Granger (EG) tests. Furthermore, this paper shows that there exist unidirectional Granger causalities running from investment, consumption and export to electricity consumption based on Vector Auto-Regression (VAR) models, which are verified robust and can be used for policy analysis.

Compared with the AC distribution network, the DC distribution network has the advantages of lower line losses, better power quality, higher reliability and being suitable for all kinds distributed generation and DC load access, etc. This paper firstly studies the models of PV and energy storage connected to the DC distribution network. Then, a new type of DC distribution network topology with hybrid DC circuit breaker is proposed. A coordinated control strategy is also proposed, which can control energy storage to improve the stability of the system. Finally, using PSCAD/EMTDC to model and simulate. The simulation results show that the proposed topology of DC distribution network and control strategy can quickly remove the fault, shorten the fault power failure time and ensure the safe and stable operation of the system, which greatly improves the operation efficiency and safety level of the power grid.

Interleukin-18 (IL-18) is a pleiotropic pro-inflammatory cytokine belonging to the IL-1 superfamily. IL-18 plays an important role in host innate and acquired immune defense, with its activity being modulatedin vivoby its naturally occurring antagonist IL-18 binding protein (IL-18BP). Recent crystal structures of human IL-18 (hIL-18) in complex with its antagonist or cognate receptor(s) have revealed a conserved binding interface on hIL-18 representing a promising drug target. An important step in this process is obtaining crystals of apo hIL-18 or hIL-18 in complex with small-molecule inhibitors, preferably under low ionic strength conditions. In this study, surface-entropy reduction (SER) and rational protein design were employed to facilitate the crystallization of hIL-18. The results provide an excellent platform for structure-based drug design.