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SLITRK1 is a critical protein involved in neural development and is associated with various neurological disorders, including Tourette Syndrome. This study investigates the structural dynamics, intrinsic disorder propensity, and pharmacological interactions of SLITRK1, with a particular focus on amino acid substitutions and their pathological implications. A comprehensive computational framework was employed, including intrinsic disorder region analysis, transmembrane topology predictions, and stability assessments of SLITRK1 variants. Integrated with reinforcement learning (RL), molecular docking and dynamics simulations were used to evaluate the pharmacotherapeutic potential of drugs commonly prescribed for Tourette Syndrome, such as Pimozide, Aripiprazole, Risperidone, and Haloperidol. Structural analyses revealed that the S656M mutation significantly alters SLITRK1's 3D conformation, biological functions, and drug binding profiles. Among the tested drugs, Aripiprazole exhibited the highest binding affinity across various SLITRK1 variants, with reinforcement learning highlighting a notable interaction with the S659K mutation. These findings were supported by Ramachandran plot and molecular dynamics analyses, which identified mutation-induced structural and dynamic changes. This study provides an integrative analysis of SLITRK1, offering insights into its role in Tourette Syndrome and laying a foundation for targeted therapeutic strategies to mitigate SLITRK1-related neurological disorders. [ABSTRACT FROM AUTHOR]

Cannabinoid and stilbenoid compounds derived from Cannabis sativa were screened against eight specific fungal protein targets to identify potential antifungal agents. The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity. This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations. The ligands with the highest binding affinities were identified, and their pharmacokinetic profiles were analyzed using ADMET analysis. The results indicate that GMP synthase exhibited the highest binding affinity with Cannabistilbene I (−9.1 kcal/mol), suggesting hydrophobic solid interactions and multiple hydrogen bonds. Similarly, Chitin Synthase 2 demonstrated significant binding with Cannabistilbene I (−9.1 kcal/mol). In contrast, ligands such as Cannabinolic acid and 8-hydroxycannabinolic acid exhibited moderate binding affinities, underscoring the variability in interaction strengths among different proteins. Despite promising in silico results, experimental validation is necessary to confirm therapeutic potential. This research lays a crucial foundation for future studies, emphasizing the importance of evaluating binding affinities, pharmacokinetic properties, and multi-target interactions to identify promising antifungal agents. The objective of this study is to identify novel antifungal agents by exploring the interactions between cannabinoids and stilbenoids derived from Cannabis sativa and eight fungal protein targets that play critical roles in fungal pathogenicity and survival. These proteins were chosen based on their essential functions of cell wall integrity, metabolic processes, stress response, and other vital cellular activities essential for the proliferation and virulence of fungal pathogens. Targeting multiple pathways aims to evaluate whether these natural compounds can effectively inhibit crucial mechanisms in fungal cells, thereby offering a potential strategy to combat antifungal resistance. Through molecular docking and dynamics simulations, this study seeks to determine these compounds' specific binding affinities, stability, and pharmacokinetic properties, laying the groundwork for future experimental validation and potential therapeutic development. [ABSTRACT FROM AUTHOR]

Abstract: Background: Importance of fluoride in dental restorative materials for preventing secondary caries. Several commercially available tooth-colored dental restorative materials, such as glass ionomer cement, resin composites, and compomers were used for this study. Aim: To evaluate the amount of fluoride release from tooth-colored restorative materials [Conventional Glass Ionomer Cement (GC Fuji II)], Resin-modified Glass Ionomer Cement (ACTIVA BioACTIVE-RESTORATIVE), and Giomer (BEAUTIFIL II LS)] using ion-selective electrode (ISE) and spectrophotometer using zirconyl alizarin red dye method. Materials and Methods: A total of 90 extracted premolars were divided into two control groups and four experimental groups. Group I: GC Fuji II/ISE; Group II: BEAUTIFIL II LS/ISE; Group III: ACTIVA BioACTIVE-RESTORATIVE/ISE; Group IV: GC Fuji II/Spectrophotometer; Group V: BEAUTIFIL II LS/Spectrophotometer; and Group VI: ACTIVA BioACTIVE-RESTORATIVE/Spectrophotometer. The amount of fluoride released was analyzed using an ion-selective elective method and spectrophotometer. The results were analyzed using a one-way analysis of variance and Scheffe post hoc tests (P ≤ 0.05). Results: Groups I and IV exhibited the highest fluoride release (1.42 and 1.12 ppm), which was statistically significant (P < 0.05) compared with Groups II and V, which showed the least using both methods. The fluoride release pattern of ACTIVA BioACTIVE (Groups III and VI) restorative was significantly lower than that of glass ionomers and showed no significant difference from the giomers groups (Groups II and IV). Conclusion: Conventional glass ionomer cement (GIC) showed the highest fluoride release followed by enhanced resin-modified GIC and giomer irrespective of the methods used. Fluoride ion concentration values obtained from the ISE method, and spectrophotometer method were comparable. Alizarin red dye can be used as an alternative to sulfanilic acid azochromotrop dye for the estimation of the release of fluoride ions from dental materials, which is known to be sensitive and much more economical compared with the latter. [ABSTRACT FROM AUTHOR]

The present study was focused on exploring the efficient inhibitors of closed state (form) of type III effector Xanthomonas outer protein Q (XopQ) (PDB: 4P5F) from the 44 phytochemicals of Picrasma quassioides using cutting-edge computational analysis. Among them, Kumudine B showed excellent binding energy (−11.0 kcal/mol), followed by Picrasamide A, Quassidine I and Quassidine J with the targeted closed state of XopQ protein compared to the reference standard drug (Streptomycin). The molecular dynamics (MD) simulations performed at 300 ns validated the stability of top lead ligands (Kumudine B, Picrasamide A, and Quassidine I)-bound XopQ protein complex with slightly lower fluctuation than Streptomycin. The MM-PBSA calculation confirmed the strong interactions of top lead ligands (Kumudine B and QuassidineI) with XopQ protein, as they offered the least binding energy. The results of absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed that Quassidine I, Kumudine B and Picrasamide A were found to qualify most of the drug-likeness rules with excellent bioavailability scores compared to Streptomycin. Results of the computational studies suggested that Kumudine B, Picrasamide A, and Quassidine I could be considered potential compounds to design novel antibacterial drugs against X. oryzae infection. Further in vitro and in vivo antibacterial activities of Kumudine B, Picrasamide A, and Quassidine I are required to confirm their therapeutic potentiality in controlling the X. oryzae infection. [ABSTRACT FROM AUTHOR]