Department of Physical Chemistry, Faculty of Chemistry, Kharazmi University, 15719-14911, Tehran, Iran.
Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, 71468-64685, Shiraz, Iran.
Langmuir. 2024 Oct 22;40(42):22136-22144. doi: 10.1021/acs.langmuir.4c02537. Epub 2024 Oct 10.
Extensive efforts have been made to improve the understanding of hard tissue regeneration, essential for advancing medical applications like bone graft materials. However, the mechanisms of bone biomineralization, particularly the regulation of hydroxyapatite growth by proteins/peptides, remain debated. Small biomolecules such as amino acids are ideal for studying these mechanisms due to their simplicity and relevance as protein/peptide building blocks. This study investigates the binding affinity of four amino acids including glycine (Gly), proline (Pro), lysine (Lys), and aspartic acid (Asp) to the hydroxyapatite (HAP) (100) surface through molecular dynamics simulations. Our findings reveal that aspartic acid exhibits the most energetically favorable binding affinity, attributed to its additional carboxylate group (-COO), which facilitates stronger interactions with Ca ions on the HAP surface compared to other amino acids with single carboxylate groups. This highlights the critical role of specific functional groups in modulating binding strength, emphasizing that the presence of multiple binding sites in amino acids enhances binding stability. Interestingly, the study also uncovers the significance of water-mediated interactions, as the compact water layer above the HAP surface acts as a barrier, complicating direct binding and underscoring the need to consider solvation effects in simulations. Glycine, due to its small size, demonstrates a unique ability to penetrate this tightly bound water monolayer, suggesting that molecular size influences binding dynamics. These simulations offer detailed insights into the atomic-level interactions, providing a deeper understanding of binding affinity and stability. These insights are pertinent for designing peptides or proteins with enhanced interactions with biomaterials, particularly in mimicking natural bone-binding processes.
人们已经做出了广泛的努力来提高对硬组织再生的理解，这对于推进骨移植物材料等医学应用至关重要。然而，骨生物矿化的机制，特别是蛋白质/肽对羟基磷灰石生长的调控，仍然存在争议。由于其简单性和作为蛋白质/肽结构单元的相关性，小分子如氨基酸非常适合研究这些机制。本研究通过分子动力学模拟研究了包括甘氨酸（Gly）、脯氨酸（Pro）、赖氨酸（Lys）和天冬氨酸（Asp）在内的四种氨基酸与羟基磷灰石（HAP）（100）表面的结合亲和力。我们的研究结果表明，天冬氨酸表现出最有利的能量结合亲和力，这归因于其额外的羧基基团（-COO），与 HAP 表面上的 Ca 离子相比，它可以促进更强的相互作用，而其他带有单个羧基基团的氨基酸则不然。这突出了特定官能团在调节结合强度方面的关键作用，强调了氨基酸中多个结合位点的存在增强了结合稳定性。有趣的是，该研究还揭示了水介导相互作用的重要性，因为 HAP 表面上方紧凑的水层充当了障碍，使直接结合变得复杂，并强调了在模拟中需要考虑溶剂化效应。由于其体积小，甘氨酸表现出独特的穿透这种紧密结合的水单层的能力，这表明分子大小会影响结合动力学。这些模拟提供了对原子级相互作用的详细了解，为理解结合亲和力和稳定性提供了更深入的认识。这些见解对于设计与生物材料具有增强相互作用的肽或蛋白质具有重要意义，特别是在模拟天然骨结合过程方面。
