2D IR SPECTROSCOPY AS A PROBE OF SOLVENT INTERACTIONS

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。 二维红外光谱结合从头算量子计算和分子动力学模拟是确定多肽结构变化动力学的一种很有前途的方法。然而，为了使这一新方法充分发挥其潜力，非常需要预测水存在下肽主链的振动光谱。现在很明显，计算不包含特定溶剂对酰胺单元的频率和跃迁偶极子的影响的光谱将不能成功地预测多肽光谱的许多基本细节。氢键和其他电荷效应引起的动态位移是很大的，需要结合模间耦合的计算来预测各种二级结构基元的特征红外光谱。 通过使用FTIR和2D IR实验的大量实验表明，对多种类型的多肽环境进行同位素选择性标记可以在逐个残基的基础上检查结构和动力学。2D IR方法的主要目标之一是简化多肽的宽带光谱，更清楚地确定其基本特征及其与水的相互作用。然而，多肽的酰胺振动形成了一组模式，每组模式的残基数量几乎都是简并的，在溶液相实验中通常不会单独识别这些组中的模式。即使是非常简化的多肽红外光谱经验理论，如果偶合常数非常大并且是易于管理的偶极-偶极类型，通常也能大致捕捉到特定二级结构的光谱形状。然而，这些方法并不声称可以预测孤立分子状态的正确光谱位移，而且它们在线形、零阶频率和波动的选择上包含随意性，对于来自不同残基的模式，这些模式可能经历与剩余二级结构或溶剂非常不同的氢键或电场。由同位素置换引起的单个残基的线性红外光谱和二维红外光谱的计算将对理论方法构成更为严格的检验。

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.