An assessment of computational methods for obtaining structural information of moderately flexible biomolecules from ion mobility spectrometry.
An assessment of computational methods for obtaining structural information of moderately flexible biomolecules from ion mobility spectrometry.
复制标题
对从离子淌度光谱法获取适度柔性生物分子结构信息的计算方法进行评估。
DOI：
10.1007/s13361-012-0339-5
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发表时间：
2012
影响因子：
3.2
通讯作者：
Clark,AuroraE
中科院分区：
文献类型：
--
作者：
Zakharova,NataliaL;Crawford,ChristinaL;Hauck,BrianC;Quinton,JacobK;Seims,WilliamF;HillJr,HerbertH;Clark,AuroraE
当与建模结合使用时，离子迁移率光谱的碰撞截面（Ω）可用于推断分析物离子的气相结构。计算确定了气相构象，并用近似方法计算了它们的Ω，并与实验数据进行了比较。虽然先前的工作主要集中在刚性小分子或大型生物分子上，但计算和实验Ω的相关性尚未对具有中间构象灵活性的分析物进行彻底检查，这些分析物构成了该领域研究的分子的很大一部分。在这里，计算Ω的计算范式已经测试了三肽WGY， YGW和YWG （Y =酪氨酸，W =色氨酸，G =甘氨酸）。实验数据表明Ωexp(YWG) > Ωexp(WGY)≈Ωexp（YGW）。利用密度泛函分析了模拟退火分子动力学（SAMD）各层构象的能量分布。这些量子力学能量分布与MD数据不一致，导致了SAMD和DFT构象之间的结构差异。后一种结构是通过重新优化SAMD几何形状而获得的，并且是重现分析物可分性实验趋势的唯一一组结构。在没有拟合Lennard Jones势的情况下，精确硬球散射法得到的数值与He漂移气体中得到的实验截面最吻合。
When utilized in conjunction with modeling, the collision cross section (Ω) from ion mobility spectrometry can be used to deduce the gas phase structures of analyte ions. Gas phase conformations are determined computationally, and their Ω calculated using an approximate method, the results of which are compared with experimental data. Though prior work has focused upon rigid small molecules or large biomolecules, correlation of computational and experimental Ω has not been thoroughly examined for analytes with intermediate conformational flexibility, which constitute a large fraction of the molecules studied in the field. Here, the computational paradigm for calculating Ω has been tested for the tripeptides WGY, YGW, and YWG (Y = tyrosine, W = tryptophan, G = glycine). Experimental data indicate that Ωexp(YWG) > Ωexp(WGY) ≈ Ωexp(YGW). The energy distributions of conformations obtained from tiers of simulated annealing molecular dynamics (SAMD) were analyzed using a wide array of density functionals. These quantum mechanical energy distributions do not agree with the MD data, which leads to structural differences between the SAMD and DFT conformations. The latter structures are obtained by reoptimization of the SAMD geometries, and are the only suite of structures that reproduce the experimental trend in analyte separability. In the absence of fitting Lennard Jones potentials that reproduce experimental results for the Trajectory Method, the Exact Hard Sphere Scattering method produced numerical values that are in best agreement with the experimental cross sections obtained in He drift gas.