MOLECULAR SIMULATIONS OF PROTEINS AT INTERFACES

蛋白质界面的分子模拟

• 批准号: 2810692
• 负责人: JULIAN TALBOT
• 金额: $ 11.49万
• 依托单位: DUQUESNE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2810692
• 关键词: adsorption; biomaterial interface interaction; computer simulation; diffusion; ionic strengths; model design /development; molecular dynamics; protein protein interaction; protein structure; solid state

The overall goal of the proposed research is to develop a quantitative molecular-level description for the adsorption of proteins at solid interfaces. Although numerous experimental studies of protein adsorption on various solid surfaces have been reported, a complete quantitative molecular picture is yet to emerge. Existing theoretical models do not account for the detailed molecular structure of the protein in the adsorption dynamics. In particular, the orientation of a protein at a solid interface, as well as its lateral mobility, is highly significant in influencing its behavior. The specific aims of this proposal are to: (1) Develop models for proteins that account for their shape and charge distribution and investigate the behavior of the models with Brownian dynamics simulation. (2) Develop Brownian dynamics code to simulate the model proteins accounting for protein-protein and protein surface interactions. (3) Examine the orientation of the adsorbed proteins as a function of surface coverage, ionic strength and temperature and the influence of the adsorption orientation on the kinetics of the process. (4) Understand the influence of lateral mobility on the adsorption kinetics and the structure of the adsorbed layer. (5) Investigate the molecular mechanism of lateral diffusion using a detailed molecular model. (6) Compare the predictions of the models with experimental data, which will allow us to refine the models or suggest new experiments. Protein adsorption plays a key role in many medical processes. For example, the performance of contact lenses and blood contacting devices is determined by the nature and the amount of the adsorbed proteins. A fundamental understanding of protein adsorption helps in the design of biocompatible surfaces for various medical applications.

提出的研究的总体目标是为蛋白质在固体界面上的吸附发展定量的分子水平描述。尽管已经报道了许多关于蛋白质在各种固体表面吸附的实验研究，但一个完整的定量分子图谱尚未出现。现有的理论模型没有考虑到吸附动力学中蛋白质的详细分子结构。特别是，蛋白质在固体界面上的取向，以及它的横向迁移，在影响其行为方面是非常重要的。本提案的具体目标是：(1)建立考虑其形状和电荷分布的蛋白质模型，并利用布朗动力学模拟研究模型的行为。(2)开发布朗动力学代码，模拟蛋白质-蛋白质和蛋白质表面相互作用的模型蛋白质。(3)研究吸附蛋白的取向与表面覆盖度、离子强度和温度的关系，以及吸附取向对过程动力学的影响。(4)了解横向迁移率对吸附动力学和吸附层结构的影响。(5)利用详细的分子模型研究横向扩散的分子机制。(6)将模型的预测与实验数据进行比较，这将使我们能够改进模型或提出新的实验建议。蛋白质吸附在许多医学过程中起着关键作用。例如，隐形眼镜和血液接触装置的性能是由吸附蛋白质的性质和数量决定的。对蛋白质吸附的基本理解有助于设计用于各种医疗应用的生物相容性表面。