Czernek Jiří, Brus Jiří
Institute of Macromolecular Chemistry, Czech Academy of Sciences, 16206 Prague, Czech Republic.
Antibiotics (Basel). 2021 Oct 18;10(10):1265. doi: 10.3390/antibiotics10101265.
Alamethicin (ALM) is an antimicrobial peptide that is frequently employed in studies of the mechanism of action of pore-forming molecules. Advanced techniques of solid-state NMR spectroscopy (SSNMR) are important in these studies, as they are capable of describing the alignment of helical peptides, such as ALM, in lipid bilayers. Here, it is demonstrated how an analysis of the SSNMR measurements can benefit from fully periodic calculations, which employ the plane-wave density-functional theory (PW DFT) of the solid-phase geometry and related spectral parameters of ALM. The PW DFT calculations are used to obtain the structure of desolvated crystalline ALM and predict the NMR chemical shift tensors (CSTs) of its nuclei. A variation in the CSTs of the amidic nitrogens and carbonyl carbons along the ALM backbone is evaluated and included in simulations of the orientation-dependent anisotropic N and C chemical shift components. In this way, the influence of the site-specific structural effects on the experimentally determined orientation of ALM is shown in models of cell membranes.
短杆菌肽A（ALM）是一种抗菌肽，常用于研究成孔分子的作用机制。先进的固态核磁共振光谱（SSNMR）技术在这些研究中很重要，因为它们能够描述螺旋肽（如ALM）在脂质双层中的排列。在此，展示了如何通过采用固相几何结构的平面波密度泛函理论（PW DFT）和ALM相关光谱参数的全周期计算，从SSNMR测量分析中获益。PW DFT计算用于获得去溶剂化结晶ALM的结构，并预测其原子核的核磁共振化学位移张量（CST）。评估了沿ALM主链的酰胺氮和羰基碳的CST变化，并将其纳入取向依赖性各向异性N和C化学位移分量的模拟中。通过这种方式，在细胞膜模型中展示了位点特异性结构效应对实验确定的ALM取向的影响。
