Background: Dental resin-based composites are widely recognized for their aesthetic appeal and adhesive properties, which make them integral to modern restorative dentistry. Despite their advantages, adhesion and biomechanical performance challenges persist, necessitating innovative strategies for improvement. This study addressed the challenges associated with adhesion and biomechanical properties in dental resin-based composites by employing molecular docking and dynamics simulation. Methods: Molecular docking assesses the binding energies and provides valuable insights into the interactions between monomers, fillers, and coupling agents. This investigation prioritizes SiO₂ and TRIS, considering their consistent influence. Molecular dynamics simulations, executed with the Forcite module and COMPASS II force field, extend the analysis to the mechanical properties of dental composite complexes. The simulations encompassed energy minimization, controlled NVT and NPT ensemble simulations, and equilibration stages. Notably, the molecular dynamics simulations spanned a duration of 50 ns. Results: SiO₂ and TRIS consistently emerged as influential components, showcasing their versatility in promoting solid interactions. A correlation matrix underscores the significant roles of van der Waals and desolvation energies in determining the overall binding energy. Molecular dynamics simulations provide in-depth insights into the mechanical properties of dental composite complexes. HEMA-SiO₂-TRIS excelled in stiffness, BisGMA-SiO₂-TRIS prevailed in terms of flexural strength, and EBPADMA-SiO₂-TRIS offered a balanced combination of mechanical properties. Conclusion: These findings provide valuable insights into optimizing dental composites tailored to diverse clinical requirements. While EBPADMA-SiO₂-TRIS demonstrates distinct strengths, this study emphasizes the need for further research. Future investigations should validate the computational findings experimentally and assess the material's response to dynamic environmental factors.

Aim: This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate (MMA), crucial components in dental materials for interim prosthetic restorations. Methodology: Molecular docking was employed to predict the binding affinities, energetics, and steric features of MMA and PMMA with selected receptors involved in bone metabolism and tissue development, including RANKL, Fibronectin, BMP9, NOTCH2, and other related receptors. The HADDOCK standalone version was utilized for docking calculations, employing a Lamarckian genetic algorithm to explore the conformational space of ligand-receptor interactions. Furthermore, molecular dynamics (MD) simulations over 100 nanoseconds were conducted using the GROMACS package to evaluate dynamic actions and structural stability. The LigandScout was utilized for pharmacophore modeling, which employs a shape-based screening approach to identify potential ligand binding sites on protein targets. Results: The molecular docking studies elucidated promising interactions between PMMA and MMA with key biomolecular targets relevant to dental applications. MD simulation results provided strong evidence supporting the structural stability of PMMA complexes over time. Pharmacophore modeling highlighted the significance of carbonyl and hydroxyl groups as pharmacophoric features, indicating compounds with favorable biocompatibility profiles. Conclusion: This study underscores the potential of PMMA in dental applications, emphasizing its structural stability, molecular interactions, and safety considerations. These findings lay a foundation for future advancements in dental biomaterials, guiding the design and optimization of materials for enhanced biocompatibility. Future directions include experimental validation of computational findings and the development of PMMA-based dental materials with improved biocompatibility and clinical performance. Graphical Abstract

Objective: The aims of this study are to identify the molecular interactions and the pharmacophore-fit of of α mangostin and its derivatives with estrogen receptor α (ERα) using computational simulation approaches to obtain new potent of anti-breast cancer. Material and Methods: Molecular docking simulation and 3D structure-based pharmacophore models were employed to identify the molecular interactions of α-mangostin and its derivatives against estrogen receptor α (ERα) (PDB ID: 3ERT). Results: The results showed that the binding energy of α-mangostin and its best derivative (AMD10) were −9.05 kcal/mol and −11.89 kcal/mol, respectively. These compounds also interacted with Thr347, Asp351, Met388, Met528, Ile424, Arg394, and Glu353. The pharmacophore-fit scores of α-mangostin and AMD10 were 83.06% and 86.46%, respectively. In addition, the absorption, distribution, metabolism and excretion (ADME) properties were predicted. Conclusion: These results showed that α-mangostin and AMD10 are promising candidates of novel anti-breast-cancer agents with antagonistic activity to ERα. Key words: α-mangostin, Estrogen receptor alpha, Molecular docking, Pharmacophore.

This study evaluates the performance of various structure prediction tools and molecular docking platforms for therapeutic peptides targeting coronary artery disease (CAD). Structure prediction tools, including AlphaFold 3, I-TASSER 5.1, and PEP-FOLD 4, were employed to generate accurate peptide conformations. These methods, ranging from deep-learning-based (AlphaFold) to template-based (I-TASSER 5.1) and fragment-based (PEP-FOLD), were selected for their proven capabilities in predicting reliable structures. Molecular docking was conducted using four platforms (HADDOCK 2.4, HPEPDOCK 2.0, ClusPro 2.0, and HawDock 2.0) to assess binding affinities and interactions. A 100 ns molecular dynamics (MD) simulation was performed to evaluate the stability of the peptide–receptor complexes, along with Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) calculations to determine binding free energies. The results demonstrated that Apelin, a therapeutic peptide, exhibited superior binding affinities and stability across all platforms, making it a promising candidate for CAD therapy. Apelin’s interactions with key receptors involved in cardiovascular health were notably stronger and more stable compared to the other peptides tested. These findings underscore the importance of integrating advanced computational tools for peptide design and evaluation, offering valuable insights for future therapeutic applications in CAD. Future work should focus on in vivo validation and combination therapies to fully explore the clinical potential of these therapeutic peptides.

For the last two years, the COVID-19 pandemic has continued to bring consternation on most of the world. According to recent WHO estimates, there have been more than 5.6 million deaths worldwide. The virus continues to evolve all over the world, thus requiring both vigilance and the necessity to find and develop a variety of therapeutic treatments, including the identification of specific antiviral drugs. Multiple studies have confirmed that SARS‐CoV‐2 utilizes its membrane-bound spike protein to recognize human angiotensin-converting enzyme 2 (ACE2). Thus, preventing spike-ACE2 interactions is a potentially viable strategy for COVID-19 treatment as it would block the virus from binding and entering into a host cell. This work aims to identify potential drugs using an in silico approach. Molecular docking was carried out on both approved drugs and substances previously tested in vivo. This step was followed by a more detailed analysis of selected ligands by molecular dynamics simulations to identify the best molecules that thwart the ability of the virus to interact with the ACE2 receptor. Because the SARS-CoV-2 virus evolves rapidly due to a plethora of immunocompromised hosts, the compounds were tested against five different known lineages. As a result, we could identify substances that work well on individual lineages and those showing broader efficacy. The most promising candidates among the currently used drugs were zafirlukast and simeprevir with an average binding affinity of –22 kcal/mol for spike proteins originating from various lineages. The first compound is a leukotriene receptor antagonist that is used to treat asthma, while the latter is a protease inhibitor used for hepatitis C treatment. From among the in vivo tested substances that concurrently exhibit promising free energy of binding and ADME parameters (indicating a possible oral administration) we selected the compound BDBM50136234. In conclusion, these molecules are worth exploring further by in vitro and in vivo studies against SARS-CoV-2.

Type 1 diabetes (T1D) is one of the world's health problems with a prevalence of 1.1 million for children and young adults under the age of 20. T1D is a health problem characterized by autoimmunity and the destruction of pancreatic cells that produce insulin. The available treatment is to maintain blood glucose within the desired normal range. To meet bolus and basal requirements, T1D patients may receive multiple daily injections (MDI) of fast-acting and long-acting insulin once or twice daily. In addition, insulin pumps can deliver multiple doses a day without causing injection discomfort in individuals with T1D. T1D patients have also monitored their blood glucose levels along with insulin replacement treatment using a continuous glucose monitor (CGM). However, this CGM has some drawbacks, like the sensor needs to be replaced after being inserted under the skin for seven days and needs to be calibrated (for some CGMs). The treatments and monitoring devices mentioned creating a lot of workloads to maintain blood glucose levels in individuals with T1D. Therefore, to overcome these problems, closed-loop artificial pancreas (APD) devices are widely used to manage blood glucose in T1D patients. Closed-loop APD consists of a glucose sensor, an insulin infusion device, and a control algorithm. This study reviews the progress of closed-loop artificial pancreas systems from the perspective of device properties, uses, testing procedures, regulations, and current market conditions.