Spectroscopy, modeling and simulation studies of peptide adsorption on polymer surfaces

蛋白质的吸附是当聚合物被引入体内时发生的第一个事件之一，并且在这种相互作用期间，蛋白质通常伴随着不可逆的形状变化。 我的研究计划的长期目标是了解蛋白质和聚合物表面相互作用之间的相互作用。我们希望随后使用这种理解（a）合理化吸附蛋白质的结构和（B）设计表面，赋予可预测的方向和构象的吸附蛋白质。 我的团队的优势在于开发光谱数据定量分析的协议，并结合实验和模拟结果，以详细了解表面构象和取向分布。 我们最近已经完成了所有的基础工作（建筑仪器，模拟数据，建立模拟技术），以表征水结构在各种疏水表面;我们还确定了一些氨基酸在这些表面的结构。 我们下一阶段的研究将集中在肽上。 为了处理这些复杂的分子，我们将利用先进的实验方法，如非线性光学相位测量，斯托克斯矢量和米勒矩阵椭圆偏振，石英晶体微天平测量。 近年来，我们也一直在发展一个平行的努力，研究相同的系统与原子分子动力学模拟。 这样的模拟结果已经丰富了我们的理解界面水和氨基酸结构，并使我们能够提出机制来解释所观察到的结构。 在我们研究计划的即将到来的阶段，我们将继续我们的模拟，现在面向表征肽二级结构的变化，因为它们遇到固体疏水表面。 我们预计，这些实验和计算方法的协同作用将使我们能够更深入地了解蛋白质如何以及为什么在疏水表面上变性。

Adsorption of proteins is one of the first events that occurs when polymers are introduced to the body, and there is often an accompanying and irreversible shape change of the protein during this interaction. The long-term objectives of my research program are to understand the interplay between protein and polymer surface interactions. We hope to subsequently use this understanding to (a) rationalize adsorbed protein structure and (b) design surfaces that impart a predictable orientation and conformation of adsorbed proteins. The strengths of my group are in developing protocols for the quantitative analysis of spectral data, and in combining experimental and simulation results to arrive at a detailed understanding of surface conformation and orientation distributions. We have recently completed all the groundwork (building instruments, modelling the data, establishing techniques for simulation) necessary to characterize water structure at various hydrophobic surfaces; we have also determined the structure of a few amino acids at these surfaces. The upcoming phase of our research will focus on peptides. To deal with these complex molecules, we will utilize sophisticated experimental approaches such as nonlinear optical phase measurements, Stokes vector & Mueller matrix ellipsometry, and quartz crystal microbalance measurements. In recent years, we have also been developing a parallel effort to study the same systems with atomistic molecular dynamics simulations. Results of such simulations have already enriched our understanding of interfacial water and amino acid structure, and have enabled us to propose mechanisms to account for the observed structures. In this upcoming phase of our research program, we will continue our simulations, now geared towards characterizing changes in peptide secondary structure as they encounter solid hydrophobic surfaces. We anticipate that the synergy in these experimental and computational approaches will enable us to contribute significantly to a deeper understanding of how and why proteins denature on hydrophobic surfaces.