Bour Petr, Keiderling Timothy A
Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo námestí 2, 16610 Praha 6, Czech Republic.
J Phys Chem B. 2005 Dec 15;109(49):23687-97. doi: 10.1021/jp054107q.
Infrared absorption and vibrational circular dichroism (IR and VCD) spectra of model fragments of TrpZip-style beta-hairpin structures are simulated using density functional theory (DFT) methods to estimate the influence of fragment size, end effects, conformational irregularities, peptide side chains, and solvent. Different fragmentation schemes, computing the strands and turn segments separately, were tested by varying the sizes of each and their respective overlaps. For suitably overlapping fragments, atomic property tensors were found to be reliably transferable, as tested by their ability to generate simulated spectra in good agreement with results from ab initio DFT computations for the entire peptide. This fragment approach significantly reduces computational times and opens up a wider range of systems that can be studied with a DFT-based approach as compared to previous methods based on uniform repeating sequences. However, vacuum calculations do not adequately represent the frequency dispersion of solvated molecules, and thus, some alternate strategies for solvation correction are explored for improving the simulation accuracy. Unlike for regular periodic secondary structure, the solvent significantly impacts the spectral shapes of hairpins, due to the different degrees of hydration of individual amide groups, which can be exposed to or shielded from water due to external vs internal hydrogen bonding. This is amplified by the shielding of selected amides from the solvent due to bulky side chains. The peptide plus solvent was structurally modeled with molecular dynamics methods, and then an electrostatic field-based parametrization correction was added to the force field and intensity tensors to compensate for the solvent dipolar field. The effect of the shielding and subsequent reordering of modes has a larger impact on VCD than IR band shapes.
利用密度泛函理论（DFT）方法模拟了TrpZip型β-发夹结构模型片段的红外吸收光谱和振动圆二色性（IR和VCD）光谱，以评估片段大小、末端效应、构象不规则性、肽侧链和溶剂的影响。通过改变每个片段的大小及其重叠部分，测试了不同的片段化方案，即分别计算链段和转角片段。对于适当重叠的片段，通过其生成模拟光谱的能力进行测试，发现原子性质张量可可靠转移，模拟光谱与整个肽的从头算DFT计算结果吻合良好。与基于均匀重复序列的先前方法相比，这种片段方法显著减少了计算时间，并开辟了更广泛的可通过基于DFT的方法进行研究的系统。然而，真空计算不能充分代表溶剂化分子的频率色散，因此，探索了一些替代的溶剂化校正策略以提高模拟精度。与规则的周期性二级结构不同，溶剂对发夹的光谱形状有显著影响，这是由于各个酰胺基团的水化程度不同，由于外部与内部氢键作用，它们可能暴露于水或被水屏蔽。由于庞大的侧链使选定的酰胺与溶剂屏蔽，这种影响会被放大。用分子动力学方法对肽加溶剂进行结构建模，然后在力场和强度张量中加入基于静电场的参数化校正，以补偿溶剂偶极场。屏蔽和随后模式重新排序的影响对VCD的影响比对IR带形状的影响更大。
