2D IR SPECTROSCOPY AS A PROBE OF SOLVENT INTERACTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 二维红外光谱结合从头计算和分子动力学模拟是一种很有前途的方法来确定肽的结构变化的动力学。然而，为了使这种新的方法，以达到其全部潜力，有一个很大的需要预测理论的振动光谱的肽骨架在水的存在下。现在很明显，不考虑特定溶剂对酰胺单元的频率和跃迁偶极子的影响的光谱计算在预测肽光谱的许多基本细节方面是不成功的。由氢键和其他电荷效应引起的动态位移是相当大的，需要结合模间耦合的计算来预测各种二级结构图案的特征红外光谱。 通过使用FTIR和2D IR实验的大量实验已经表明，许多类型的肽环境的同位素选择性标记可以允许在逐个残基的基础上检查结构和动力学。二维红外方法的主要目标之一是简化肽的宽带光谱，并更清楚地定义潜在的特征及其与水的相互作用。然而，肽的酰胺振动形成模式组，每个模式组具有残基数量的近简并性，并且这些组中的模式通常在溶液相实验中不单独识别。即使是非常简化的肽红外光谱的经验理论，往往捕捉近似的光谱形状的特定二级结构，如果耦合常数发生非常大，容易管理的偶极-偶极型。然而，这种方法并不声称预测正确的光谱位移从孤立的分子状态，它们包含任意选择其线形，零阶频率和波动，在任何耦合之前，从不同的残基，可能会经历非常不同的氢键或电场从剩余的二级结构或溶剂的模式。通过同位素置换移位的单个残基的线性和2D IR光谱的计算将构成对理论方法的更严格的测试。

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. Two-dimensional infrared (2D IR) spectroscopy in conjunction with ab initio quantum computations and molecular dynamics simulations is a promising approach to determining the dynamics of structure changes of peptides. However, in order to allow this novel approach to reach its full potential, there is a great need for predictive theories of the vibrational spectra of the peptide backbone in the presence of water. It is now evident that calculations of spectra that do not incorporate specific solvent effects on the frequencies and transition dipoles of the amide unit will not be successful in predicting many essential details of the spectra of peptides. The dynamic shifts caused by hydrogen bonding and other charge effects are substantial and need to be combined with computations of intermode coupling to predict the characteristic infrared spectra of the various secondary structure motifs. It has been shown through numerous experiments using FTIR and 2D IR experiments that isotope selective labeling of many types of peptide environments can permit structure and dynamics to be examined on a residue-by-residue basis. One of the main goals of 2D IR methods is to simplify the broadband spectra of peptides and define more clearly the underlying features and their interactions with water. However, the amide vibrations of peptides form groups of modes, each having a near degeneracy of the number of residues, and the modes in these groups are not normally identified separately in solution phase experiments. Even very simplified empirical theories of peptide IR spectra often capture approximately the spectral shapes for particular secondary structures if the coupling constants happen to be very large and of the easily manageable dipole-dipole type. However, such approaches do not claim to predict the correct spectral shifts from isolated molecule states, and they contain arbitrariness in the choice of their line shapes, zero-order frequencies and fluctuations, prior to any coupling, for modes from different residues that might be experiencing very different hydrogen bonding or electric fields from the remaining secondary structure or the solvent. The computation of linear and 2D IR spectra of individual residues shifted by isotope replacement would constitute a much more stringent test of the theoretical methods.