Department of Dental Technology, COAMS, King Khalid University, Abha, Saudi Arabia.
Department of Restorative Dentistry, College of Dentistry, King Khalid University, Abha, Saudi Arabia.
J Mater Sci Mater Med. 2024 Jun 4;35(1):28. doi: 10.1007/s10856-024-06799-7.
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.
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.
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.
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.
本研究旨在全面评估聚甲基丙烯酸甲酯（PMMA）及其单体甲基丙烯酸甲酯（MMA）的生物相容性和毒性特征，这两种物质是牙科临时修复体材料中的关键成分。
采用分子对接技术预测 MMA 和 PMMA 与参与骨代谢和组织发育的选定受体（包括 RANKL、纤维连接蛋白、BMP9、NOTCH2 和其他相关受体）的结合亲和力、能量和空间特征。使用 HADDOCK 独立版本进行对接计算，采用拉马克遗传算法探索配体-受体相互作用的构象空间。此外，使用 GROMACS 软件包进行 100 纳秒以上的分子动力学（MD）模拟，以评估动态作用和结构稳定性。利用 LigandScout 进行药效团建模，该方法采用基于形状的筛选方法来识别蛋白质靶标上的潜在配体结合位点。
分子对接研究阐明了 PMMA 和 MMA 与牙科应用相关的关键生物分子靶标之间有前景的相互作用。MD 模拟结果提供了强有力的证据，表明 PMMA 复合物在时间上具有结构稳定性。药效团建模突出了羰基和羟基作为药效团特征的重要性，表明具有良好生物相容性特征的化合物。
本研究强调了 PMMA 在牙科应用中的潜力，强调了其结构稳定性、分子相互作用和安全性考虑。这些发现为牙科生物材料的未来发展奠定了基础，指导了具有增强生物相容性和临床性能的 PMMA 基牙科材料的设计和优化。未来的方向包括计算发现的实验验证以及开发具有改善的生物相容性和临床性能的基于 PMMA 的牙科材料。
