HYBRIDIZED DENTIN: BIOMIMETIC MODELING AND OPTIMIZATION

描述（由申请人提供）：牙本质修复界面的强度、耐久性和抗渗透性在牙齿修复过程中至关重要，因为修复后该界面的任何破坏都会为毒素和细菌进入牙髓开辟途径。近年来，在结合过程中，粘接剂渗透到非物质化的牙本质中，从而在该界面形成杂交牙本质的研究得到了相当多的关注。分析和形态学研究表明，杂交层是胶原原纤维和粘附材料的亲密分子混合物。在粘合过程中，粘合剂单体被允许渗透到由脱矿打开的牙本质亚表面的空隙中。在渗透到牙本质下表面的过程中，单体与胶原原纤维相互作用，随后聚合为杂交结构提供强度。光谱研究还不能完全表征界面结构，特别是粘合剂-胶原相互作用。不同的研究者根据相似或不同的实验得出了相互矛盾的结论。研究杂交牙本质的一种创新方法是通过计算机模拟来探测潜在的相互作用。本应用程序中概述的研究是胶原蛋白和单体结构及其相互作用的计算机辅助仿生建模新方法的延续。申请人在一项由美国国立卫生研究院通过AREA拨款支持的可行性研究中开发了该方法。在本研究中，三螺旋胶原受体模型结构的优化构象状态和单体分子及其相互作用产生的复合物将被可视化，并在溶剂的存在下在原子水平上分析它们的相互作用。配体受体分子反应位点的立体和静电互补性将被表征。胶原-配体复合物形成的相互作用能将被计算为范德华、静电和氢键相互作用的累积效应。这些能量贡献将被分析，以确定每个单体的主要相互作用模式。配体与胶原蛋白之间的结合研究将通过以下方式进行：1)我们开发的一种新型免疫化学结合试验；2)等温滴定量热法，并计算相关的相互作用能值。

DESCRIPTION (provided by applicant): The strength, durability and impermeability of the dentin-restoration interface are of critical importance during tooth restoration because any post-restoration breakdown of this interface opens up pathways for toxins and bacteria to penetrate into the pulp. In recent years, there has been considerable focus on the formation of hybridized dentin at this interface by the infiltration of adhesives into the dematerialized dentin during bonding. Analytical and morphological studies have revealed the hybrid layer to be an intimate molecular mixture of collagen fibrils and adhesive material. During bonding adhesive monomers are allowed to permeate into the vacant spaces on the subsurfaces of dentin opened up by demineralization. During infiltration into the sub-surface of dentin, the monomer interacts with collagen fibrils and is subsequently polymerized to provide strength to the hybridized structure. Spectrographic investigations have not been able to fully characterize the interface structure, especially the adhesive-collagen interaction. Different investigators have arrived at conflicting conclusions based on similar or different experiments. One innovative approach to study hybridized dentin is to probe potential interactions through computer simulations. The research outlined in this application is a continuation of a novel method of computer-aided biomimetic modeling of collagen and monomer structures and their interactions. The applicant developed this method in a feasibility study supported by the NIH through an AREA grant. In this study, optimized conformational states of model structures of the triple helical collagen receptor and the monomer molecules and the complex generated by their interaction will be visualized and their interactions in the presence of a solvent analyzed at the atomic level. The steric and electrostatic complementarity of the reactive sites of the ligand receptor molecules will be characterized. The interaction energy for the formation of the collagen-ligand complex will be calculated as the cumulative effect of van der Waals, electrostatic and hydrogen bonding interactions. These energy contributions will be analyzed to determine the predominant mode of interaction for each monomer. Binding studies between the ligands and collagen will be conducted by:1) a novel immunochemical binding assay developed by us; and 2) isothermal titration calorimetry, and related to computed interaction energy values.