Interaction Sites Research Articles

Biopolymer composites based on ultrasound/plasma‐modified fiber waste and polybutylene adipate terephthalate (PBAT): Physicochemical and functional performance

AbstractA strategy for a circular economy is to reuse and modify agricultural wastes through green methodologies, which can be employed as high‐value raw materials to produce sustainable materials. Thus, polybutylene adipate terephthalate (PBAT) composites containing plasma (P) and ultrasound/plasma (UP) modified Agave fibers (AF) were prepared by the melt mixing process. The effect of content (10% and 20%) and type of fiber on the processing, structural, mechanical, and water barrier performance of PBAT composites was assessed. FTIR analysis exhibited the presence of O‐Si‐O groups in all composites containing modified AF, indicating the presence of nanometric hexamethyldisiloxane (HMDSO) coating on the fiber surface. The addition of modified AF into PBAT polymer promoted higher torque levels and specific energy during the composites processing, indicating higher matrix‐fiber interactions that hindered the free flow of the polymeric chains. Nevertheless, SEM, DSC, and crystallinity results revealed that PBAT‐AFUP composites exhibited more homogeneous surfaces and ordered structures that promoted higher entanglement between modified fibers and the PBAT matrix and restricted the binding sites for water interaction as changes in tensile modulus (from 90 to 163 MPa) and water contact angle (from 63 to 77°) indicated. These findings show that modified Agave fibers are a sustainable raw material that can be easily processed to produce soft and hydrophobic PBAT‐based composites.Highlights The fiber type determined the functional performance of the PBAT composites The modified fibers increased the entanglement of composite chains UP‐modified fibers improved the water barrier performance of the PBAT matrix

Home and Journey in Experiences of the Eastern Orthodox Divine Liturgy

This paper explores the experiential reality surrounding the Divine Liturgy, a Byzantine rite in Orthodox Christianity that has remained central to Eastern practice globally since Late Antiquity. The article draws on multi-sited ethnography in the glocal context of the Orthodox Church of Finland (OCF), a national church of minority and a site of multicultural interaction. Our analysis shows participants articulate their experiences with the Liturgy in an epistemology of interiority by which (1) they constantly, if unevenly, and agentically engage with the Liturgy in a form of individual, vernacular artistry. This interiority is (2) both sensorial and interpretative, and (3) ambivalently grounded in motifs of being “at home” and, at the same time, “on a journey.” That is, participants from different backgrounds make a connection to the Liturgy both as a spiritual and a literal home, relating to different elements—Finnish, Karelian, Byzantine, and Church Slavonic—in its ritualistic aesthetics. At the same time, Liturgy emerges as a perpetual journey of new openings and glimpses, informed by past experiences and life trajectories, and participants relate to these two aspects simultaneously.

Elucidating the mechanisms of ultrasound treatment combined with κ-carrageenan addition enhancing the gelling properties of heat-induced myofibrillar protein gel

This work investigated the effect of ultrasound (US) treatment synergized with κ-carrageenan (KC) on the gel properties, structural characteristics and microstructures of myofibrillar protein (MP) gel. The results demonstrated that simply adding KC enhanced the gel strength and water holding capacity (WHC) of MP gels. Moreover, the gel strength and WHC of MP gels were increased by 56.67 % and 76.19 % via 20 min US treatment synergized with KC, which was mainly attributed to the changes in sulfhydryl content, surface hydrophobicity, and fluorescence intensity of MP gels. Based on the results of molecular docking and secondary structure, it can be hypothesized that the synergistic effect resulted in the rearrangement of the proteins, which altered the interaction site between MP gels and KC, accompanied by stronger binding. Furthermore, the microstructural results indicated that moderate US treatment (20 min) facilitated the production of a more compact and denser MP gels matrix with uniformly sized and distributed pores. However, excessive US treatment (40 and 50 min) caused the MP gels to form looser and disordered gel structure, which reduced the gel strength and WHC. This study suggested that combining of US and KC was a potential tactic to enhance the gelling properties of heat-induced MP gels.

Modulating the electron interaction of Cu-Ni hybrid sites for boosting photocatalytic hydrogen evolution over Al-doped SrTiO3

Cocatalysts play a pivotal role in enhancing the efficiency of photocatalytic water splitting. In this study, we introduced a novel and straightforward pre-impregnation strategy to anchor a CuNi dual cocatalyst onto the surface of Al-doped SrTiO3 (Al-STO), coupled with photodeposition. This approach led to a remarkable 11.07-fold (77.5 µmol/h) increase in hydrogen evolution performance compared to the conventional photodeposition method for decorating with CuNi dual cocatalysts. Not only that, after the 18 h cycle experiment, the catalyst still maintains high activity and high stability similar to that of precious metals, which overcomes the defects of poor stability and short life of non-precious metals. This strategy capitalizes on the pre-adsorption of cocatalyst precursor ions on the Al-STO support via impregnation, enhancing both the adsorption energy and capacity between the precursor ions and the active sites. Detailed characterizations have revealed a strong electronic interaction within the Cu-Ni structure and improved interfacial coupling between CuNi and Al-STO. This not only significantly promotes charge separation and transfer but also provides a plethora of active sites for the photocatalytic generation of H2. Moreover, extensive theoretical calculations have provided deep insights into the reaction mechanism of the CuNi system and elucidated the reasons behind the varying degrees of activity enhancement across different cocatalyst architectural systems.

Polymer free volume and its connection to the entanglement length and the plateau modulus via polymer mode-coupling theory and equation of state

Using a many-chain system of Gaussian chains interacting with each other through the Lennard-Jones (LJ) potential, we demonstrate that there exists a connection between polymer fractional free volume (f) and the entanglement chain length (Ne). Here, f is determined by the generic van der Waals (GvdW) equation of state using the intermolecular radial distribution function [g(r)] of the Gaussian chain generated by the polymer reference interaction sites model while Ne by the polymer mode-coupling theory (PMCT) for strongly coupled macromolecules. The key concept in PMCT is that intermolecular forces experienced by a bead in a chain surrounded by other chains are strongly coupled to the site specific intramolecular radial distribution function. The calculated Gp and η of polyethylene with chain lengths from 500 to 2000 interacting with one another through the LJ potential agree well with experiment and molecular dynamics simulation.

New Selective Inhibitors of α‐Glucosidase for the Treatment of Type 2 Diabetes Mellitus

AbstractType 2 diabetes mellitus is a metabolic dreadful disease caused by an uncontrolled glucose level in the bloodstream, particularly high after a meal. Inhibitors of glucosidases, involved in the digestion of carbohydrates, can regulate this post‐prandial increase in glucose concentration. The traditional drugs act as competitive inhibitors of both pancreatic α‐amylase and α‐glucosidases and this unselective inhibition is behind severe gastrointestinal side effects related to the concomitant inhibition of α‐amylase. We described herein some perglycosylated cyclodextrins as efficient and selective inhibitors of α‐glucosidase with low micromolar IC50 (3.64‐7.98 μM) compared to the acarbose (IC50 212 μM), clinically used for patients suffering from type 2 diabetes. On the other hand, they do not inhibit α‐amylase (IC50>500 μM). Structure/activity relationship rationalization suggests multiple interactions between the described inhibitors and α‐glucosidase, which support the existence of both active site and allosteric interactions.

Insight into the Effect of Submicellar Concentrations of Sodium Deoxycholate on the Structure, Stability, and Activity of Bovine and Human Serum Albumin: An Interesting Comparison between Single and Double Tryptophan Proteins.

The progressive escalation in the applications of bile salts in diverse fields has triggered research on their interaction with various biological macromolecules, especially with proteins. A proper understanding of the interaction process of bile salts, particularly in the lower concentrations range, with the serum albumin seems important since the normal serum concentration of bile salts is approximately in the micromolar range. The current study deals with a comprehensive and comparative analysis of the interaction of submicellar concentrations of sodium deoxycholate (NaDC) with two homologous transport proteins: bovine serum albumin (BSA) and human serum albumin (HSA). HSA and BSA with one and two tryptophans, respectively, provide the opportunity for an interesting comparison of tryptophan fluorescence behavior on interaction with NaDC. The study suggests a sequential interaction of NaDC in three discrete stages with the two proteins. A detailed study using warfarin and ibuprofen as site markers provides information about the sites of interaction, which is further confirmed by inclusive molecular dynamics simulation analysis. Moreover, the comparison of the thermodynamics and stability of the NaDC-serum albumin complexes confirms the stronger interaction of NaDC with BSA as compared to that with HSA. The differential interaction between the bile salt and the two serum albumins is further established from the difference in the extent of decrease in the esterase-like activity assay of the proteins in the presence of NaDC. Therefore, the present study provides important insight into the effect of submicellar concentrations of NaDC on the structure, stability, and activity of the two homologous serum albumins and thus can contribute not only to the general understanding of the complex nature of serum albumin-bile salt interactions but also to the design of more effective pharmaceutical formulations in the field of drug delivery and biomedical research.

Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity

The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.

Molecular mechanism of efficient separation of isopropyl alcohol and isooctane by extractive distillation

In this paper, a method of extracting isopropyl alcohol and isooctane system from industrial wastewater of fuel oil by extractive distillation is proposed to realize resource utilization of waste and reduce environmental pollution. Isooctane and isopropyl alcohol are both products obtained from petroleum refining, which are widely used in many fields. In this study, the quantum chemical was used to determine that glycerol (Gl) and N, N-dimethylacetamide (DMAC) were the best extractants to separate Isopropanol and isopropyl alcohol. The intermolecular electrostatic interaction and reaction site between the extractant and the system were determined by electrostatic potential (ESP) analysis. Inter-complex compounds and weak interactions were analyzed by interaction region indicator (IRI). The independent gradient model based on Hirschfeld partition (IGMH) was used to visualize the electron density of the molecule. Meanwhile, the simulation process of azeotropic mixture separation of IPA and ISO by extractive distillation was established, and the process was optimized by a sequential iterative method. The economic and environmental were used to evaluate and analyze the process, and the azeotropic mixture separation was realized. Compared with Gl, the extractive distillation separation of isopropyl alcohol and isooctane by DMAC reduces the total annual cost by 5 %, energy consumption, and reduces the greenhouse gas emissions by 1 %, and has greater environmental protection and economic benefits. This work is guided by quantum chemical calculation and reveals the interaction mechanism of solvent separation azeotropic mixture from the microscopic level, which provides an important reference value for realizing high efficiency, energy saving, and green separation of azeotropic mixture in industry.

TRIM72 restricts lyssavirus infection by inducing K48-linked ubiquitination and proteasome degradation of the matrix protein.

The tripartite motif (TRIM) protein family is the largest subfamily of E3 ubiquitin ligases, playing a crucial role in the antiviral process. In this study, we found that TRIM72, a member of the TRIM protein family, was increased in neuronal cells and mouse brains following rabies lyssavirus (RABV) infection. Over-expression of TRIM72 significantly reduced the viral titer of RABV in neuronal cells and mitigated the pathogenicity of RABV in mice. Furthermore, we found that TRIM72 over-expression effectively prevents the assembly and/or release of RABV. In terms of the mechanism, TRIM72 promotes the K48-linked ubiquitination of RABV Matrix protein (M), leading to the degradation of M through the proteasome pathway. TRIM72 directly interacts with M and the interaction sites were identified and confirmed through TRIM72-M interaction model construction and mutation analysis. Further investigation revealed that the degradation of M induced by TRIM72 was attributed to TRIM72's promotion of ubiquitination at site K195 in M. Importantly, the K195 site was found to be partially conserved among lyssavirus's M proteins, and TRIM72 over-expression induced the degradation of these lyssavirus M proteins. In summary, our study has uncovered a TRIM family protein, TRIM72, that can restrict lyssavirus replication by degrading M, and we have identified a novel ubiquitination site (K195) in lyssavirus M.

Analyzing isothermal crystallization of poly(lactic acid)/polyol systems: Correlated DSC and simulation studies

The isothermal crystallization behavior and kinetics of poly(l-lactic acid) (PLLA) melt-blended small amounts (0.7%–1%) of polyols (D-mannitol, D-sorbitol, and xylitol) were investigated by differential scanning calorimetry (DSC), and the interaction between polyols and PLLA was clarified via multiscale theoretical simulations. The decreased peak crystallization time and full width at half peak maximum (FWHM) of polyol-modified PLLA indicates that the crystallization capability of PLLA was improved, and the process was accelerated. The crystallinity remains unchanged before and after modification at the same temperature. The Avrami exponent (n) is largely unaffected, indicating that polyols as nucleation accelerants hardly alter the nucleation and growth mechanisms of PLLA crystallization. The outputs of long-term molecular dynamics simulations were fulfilled toward large-scale periodic models for three polyol-PLLA models that involved over 20,000 atoms. Therein, the interaction energies and the derived radial distribution function (RDF) implied the hydrogen bonding occurred between polyol and PLLA. To visualize the interaction sites between the polyol and PLLA, the frontier orbital distributions of the polyols were further calculated according to density functional theory (DFT). Theoretical evidence suggests that polyols improve the crystallization capability of PLLA by hydrogen bonding between the terminal hydroxyl group and the carbonyl oxygen of PLLA.

Cisplatin Nephrotoxicity Is Critically Mediated by the Availability of BECLIN1.

Cisplatin nephrotoxicity is a critical limitation of solid cancer treatment. Until now, the complex interplay of various pathophysiological mechanisms leading to proximal tubular cell apoptosis after cisplatin exposure has not been fully understood. In our study, we assessed the role of the autophagy-related protein BECLIN1 (ATG6) in cisplatin-induced acute renal injury (AKI)-a candidate protein involved in autophagy and with putative impact on apoptosis by harboring a B-cell lymphoma 2 (BCL2) interaction site of unknown significance. By using mice with heterozygous deletion of Becn1, we demonstrate that reduced intracellular content of BECLIN1 does not impact renal function or autophagy within 12 months. However, these mice were significantly sensitized towards cisplatin-induced AKI, and by using Becn1+/-;Sglt2-Cre;Tomato/EGFP mice with subsequent primary cell analysis, we confirmed that nephrotoxicity depends on proximal tubular BECLIN1 content. Mechanistically, BECLIN1 did not impact autophagy or primarily the apoptotic pathway. In fact, a lack of BECLIN1 sensitized mice towards cisplatin-induced ER stress. Accordingly, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) blunted cisplatin-induced cell death in Becn1 heterozygosity. In conclusion, our data first highlight a novel role of BECLIN1 in protecting against cellular ER stress independent from autophagy. These novel findings open new therapeutic avenues to intervene in this important intracellular stress response pathway with a promising impact on future AKI management.

Effect of resveratrol on herpesvirus encephalitis: Evidences for its mechanisms of action

BackgroundHerpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PurposeThis study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. MethodsThe antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90β) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. ResultsResveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90β, thus disrupting the HSP90β-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. ConclusionResveratrol acted as a non-classical HSP90β inhibitor, binding to the STING-HSP90β interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90β and resveratrol-mediated inhibition of HSP90β as a potential antiviral approach.

High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules.

Flaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small molecule inhibitors to disrupt the promoter function. To facilitate the identification of small molecule binding sites in flavivirus SLA, we determined high-resolution structures of the bottom and top stems of ZIKV SLA, which contain a single U- or G-bulge, respectively. Both bulge nucleotides exhibit multiple orientations, from folded back on the adjacent nucleotide to flipped out of the helix, and are stabilized by stacking or base triple interactions. These structures suggest that even a single unpaired nucleotide can provide flexibility to RNA structures, and its conformation is mainly determined by the stabilizing chemical environment. To facilitate discovery of small molecule inhibitors that interfere with the functions of ZIKV SLA, we screened and identified compounds that bind to the bottom and top stems of ZIKV SLA.

Water Film Structure and Wettability of Different Quartz Surfaces: Hydrogen Bonding Across Various Cutting Planes.

Quartz is ubiquitous in subsurface formations. The crystal faces have different atomic arrangements. Knowledge of the molecular structures on the surface of quartz is key in many processes. Molecular dynamics simulations are conducted to investigate the atomic arrangement effect on the water film structure, ion adsorption, and wettability at three different α-quartz surfaces. The interfacial structures depend on the quartz surface. Intrasurface hydrogen bonding between surface silanols differs in the α-quartz surface. At the (0001) surface, the OH density is 9.58 nm-2, consisting of Q2 units with two hydroxyl groups per silicone atom. At the (101̅0)-β surface, the OH density is 7.54 nm-2, consisting of Q3 units with one hydroxyl group per silicone atom; there is significant intrasurface hydrogen bonding. At the (101̅0)-α surface, the OH density is 7.54 nm-2, consisting of Q2 units; however, there is little intrasurface hydrogen bonding. The intrasurface hydrogen bonding results in the exposure of hydrogen-bond acceptors to the aqueous phase, causing water molecules to have an H-up (hydrogen toward surface) orientation. This orientation can be found at the (0001) and (101̅0)-β surfaces; it is related to the degree of ordering at the surface. The ordering at the (0001) and (101̅0)-β surfaces is higher than that at the (101̅0)-α surface. In aqueous systems with ions, cation adsorption is the most dominant at the (0001) surface due to the largest surface density of the intrasurface hydrogen bonding, providing interaction sites for cations to be adsorbed. We observe a pronounced decrease in water film thickness from the ions at the (0001) surface only, likely due to significant cation adsorption. In this work, we demonstrate that the hydrogen-bond network, which varies from the plane cut, affects the water film structure and ion adsorption. The contact is nearly zero despite the changes in the film thickness and molecular structure at the temperature of 318 K.

Solvent Distribution Effects on Quantum Chemical Calculations with Quantum Computers.

We present a combination of three-dimensional reference interaction site model self-consistent field (3D-RISM-SCF) theory and the variational quantum eigensolver (VQE) to consider the solvent distribution effects within the framework of quantum-classical hybrid computing. The present method, 3D-RISM-VQE, does not include any statistical errors from the solvent configuration sampling owing to the analytical treatment of the statistical solvent distribution. We apply 3D-RISM-VQE to compute the spatial distribution functions of solvent water around a water molecule, the potential and Helmholtz energy curves of NaCl, and to analyze the Helmholtz energy component and related properties of H2O and NH4+. Moreover, we utilize 3D-RISM-VQE to analyze the extent to which solvent effects alter the efficiency of quantum calculations compared with calculations in the gas phase using the L1-norms of molecular electronic Hamiltonians. Our results demonstrate that the efficiency of quantum chemical calculations on a quantum computer in solution is virtually the same as that in the gas phase.

Fast and scalable querying of eukaryotic linear motifs with gget elm.

Eukaryotic linear motifs (ELMs), or Short Linear Motifs, are protein interaction modules that play an essential role in cellular processes and signaling networks and are often involved in diseases like cancer. The ELM database is a collection of manually curated motif knowledge from scientific papers. It has become a crucial resource for investigating motif biology and recognizing candidate ELMs in novel amino acid sequences. Users can search amino acid sequences or UniProt Accessions on the ELM resource web interface. However, as with many web services, there are limitations in the swift processing of large-scale queries through the ELM web interface or API calls, and, therefore, integration into protein function analysis pipelines is limited. To allow swift, large-scale motif analyses on protein sequences using ELMs curated in the ELM database, we have extended the gget suite of Python and command line tools with a new module, gget elm, which does not rely on the ELM server for efficiently finding candidate ELMs in user-submitted amino acid sequences and UniProt Accessions. gget elm increases accessibility to the information stored in the ELM database and allows scalable searches for motif-mediated interaction sites in the amino acid sequences. The manual and source code are available at https://github.com/pachterlab/gget.

Photo-affinity and Metabolic Labeling Probes Based on the Opioid Alkaloids.

The opioids are powerful analgesics yet possess contingencies that can lead to opioid-use disorder. Chemical probes derived from the opioid alkaloids can provide deeper insight into the molecular interactions in a cellular context. Here, we designed and developed photo-click morphine (PCM-2) as a photo-affinity probe based on morphine and dialkynyl-acetyl morphine (DAAM) as a metabolic acetate reporter based on heroin. Application of these probes to SH-SY5Y, HEK293T, and U2OS cells revealed that PCM-2 and DAAM primarily localize to the lysosome amongst other locations inside the cell by confocal microscopy and chemical proteomics. Interaction site identification by mass spectrometry revealed the mitochondrial phosphate carrier protein, solute carrier family 25 member 3, SLC25A3, and histone H2B as acylation targets of DAAM. These data illustrate the utility of chemical probes to measure localization and protein interactions in a cellular context and will inform the design of probes based on the opioids in the future.

Role of the leucine-rich repeat protein kinase 2 C-terminal tail in domain cross-talk.

Leucine-rich repeat protein kinase 2 (LRRK2) is a multi-domain protein encompassing two of biology's most critical molecular switches, a kinase and a GTPase, and mutations in LRRK2 are key players in the pathogenesis of Parkinson's disease (PD). The availability of multiple structures (full-length and truncated) has opened doors to explore intra-domain cross-talk in LRRK2. A helix extending from the WD40 domain and stably docking onto the kinase domain is common in all available structures. This C-terminal (Ct) helix is a hub of phosphorylation and organelle-localization motifs and thus serves as a multi-functional protein : protein interaction module. To examine its intra-domain interactions, we have recombinantly expressed a stable Ct motif (residues 2480-2527) and used peptide arrays to identify specific binding sites. We have identified a potential interaction site between the Ct helix and a loop in the CORB domain (CORB loop) using a combination of Gaussian accelerated molecular dynamics simulations and peptide arrays. This Ct-Motif contains two auto-phosphorylation sites (T2483 and T2524), and T2524 is a 14-3-3 binding site. The Ct helix, CORB loop, and the CORB-kinase linker together form a part of a dynamic 'CAP' that regulates the N-lobe of the kinase domain. We hypothesize that in inactive, full-length LRRK2, the Ct-helix will also mediate interactions with the N-terminal armadillo, ankyrin, and LRR domains (NTDs) and that binding of Rab substrates, PD mutations, or kinase inhibitors will unleash the NTDs.

PENINGKATAN PROMOSI DAN PENGARSIPAN DIGITAL SANGGAR SENI TARI DAN BUDAYA SAWO KECIK MELALUI PEMBUATAN WEBSITE AI

ABSTRACT This community service activity aimed to develop and launch an artificial intelligence (AI)-based website as a promotional media and digital archive for the Cirebon Sawo Kecik Dance and Culture Art Studio. This is due to the need for this dance studio to increase its exposure in the digital world and archive works of art. In creating this website, a needs analysis was carried out, website development with AI integration, as well as training for studio members. From the results of implementing this activity, it was found that an interactive website can accommodate event promotion, adjust content to visitor preferences, and collect digital archive data of works of art. This community service activity also helped dance studios increasing their visibility online. Therefore, the application of AI technology in the form of a website has helped the Sawo Kecik Dance and Cultural Arts Studio achieve the studio's digital promotion and archiving goals well.