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

蛋白质的吸附是聚合物被引入体内时发生的第一个事件，在这个相互作用过程中，蛋白质经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。我们希望随后利用这一理解来(A)使吸附的蛋白质结构合理化，并(B)设计给予吸附蛋白质的可预测的取向和构象的表面。我的团队的优势在于开发了光谱数据定量分析的协议，并将实验和模拟结果结合在一起，以达到对表面构象和取向分布的详细了解。我们最近已经完成了表征各种疏水表面的水结构所需的所有基础工作(建造仪器、建立数据模型、建立模拟技术)；我们还确定了这些表面上几个氨基酸的结构。我们下一阶段的研究将集中在多肽上。为了处理这些复杂的分子，我们将利用复杂的实验方法，如非线性光学相位测量，斯托克斯矢量和米勒矩阵椭偏测量，以及石英晶体微天平测量。近年来，我们也一直在开展一项平行的努力，用原子分子动力学模拟来研究相同的系统。这些模拟的结果已经丰富了我们对界面水和氨基酸结构的理解，并使我们能够提出解释观察到的结构的机制。在即将到来的研究计划阶段，我们将继续我们的模拟，现在的目标是描述当它们遇到固体疏水表面时多肽二级结构的变化。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.