SPECTRAL SIGNATURES OF STRUCTURAL INHOMOGENEITIES ON FOLDING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在水溶液中形成稳定螺旋的丙氨酸短肽一直是一些实验的焦点，这些实验旨在通过红外光谱的温度依赖性来探索螺旋形成的热力学和动力学。基于丙氨酸的多肽在低温下高度α-螺旋，并经历热变性。到目前为止，试图真实地模拟它们在展开时因温度而引起的红外光谱变化的尝试，一直受到缺乏关于结构不均一性及其在变性过程中演变的细节的阻碍。 在计算能力和算法方面的最新进展使多肽在显式水溶液中的自由能景观的计算成为可能。使用副本交换分子动力学(REMD)方法的模拟正在进行，以在广泛的温度范围内对螺旋肽的整体构型进行采样。这些系综提供了深入了解由于氢键和折叠/展开的溶剂化螺旋的构象变化而导致的潜在不均一性是如何在红外光谱中表现出来的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Short alanine-based peptides that form stable helices in aqueous solution have been the focal point of several experiments aimed at probing the thermodynamics and kinetics of helix formation by means of the temperature dependence of their IR spectra. Alanine-based peptides are highly alpha-helical at low temperature and undergo thermal denaturation. Until now attempts to realistically model temperature-induced changes in their IR spectra upon unfolding have been hampered by a lack of detail regarding structural inhomogeneity and its evolution during denaturation. Recent advances in computational power and algorithms have made possible the calculation of the free-energy landscape of peptides in explicit aqueous solvent. Simulations using the replica-exchange molecular dynamics (REMD) methodology are being performed to sample the ensemble of configurations of a helical peptide over a broad range of temperatures. These ensembles provide insight into how the underlying inhomogeneities due to H-bonding and conformational variability of a folding/unfolding solvated helix are manifested in an IR spectrum.