Ninković Dragan B, Malenov Dušan P, Petrović Predrag V, Brothers Edward N, Niu Shuqiang, Hall Michael B, Belić Milivoj R, Zarić Snežana D
Science Program, Texas A&M University at Qatar, Texas A&M Engineering Building, Education City, Doha, Qatar.
Innovation Center, Department of Chemistry, University of Belgrade, Studentski trg 12-16, 11000, Belgrade, Serbia.
Chemistry. 2017 Aug 16;23(46):11046-11053. doi: 10.1002/chem.201701351. Epub 2017 Jul 24.
The role of aromatic and nonaromatic amino acids in amyloid formation has been elucidated by calculating interaction energies between β-sheets in amyloid model systems using density functional theory (B3LYP-D3/6-31G*). The model systems were based on experimental crystal structures of two types of amyloids: (1) with aromatic amino acids, and (2) without aromatic amino acids. Data show that these two types of amyloids have similar interaction energies, supporting experimental findings that aromatic amino acids are not essential for amyloid formation. However, different factors contribute to the stability of these two types of amyloids. In the former, the presence of aromatic amino acids significantly contributes to the strength of interactions between side chains; interactions between aromatic and aliphatic side chains are the strongest, followed by aromatic-aromatic interactions, while aliphatic-aliphatic interactions are the weakest. In the latter, that is, the amyloids without aromatic residues, stability is provided by interactions of aliphatic side chains with the backbone and, in some cases, by hydrogen bonds.
通过使用密度泛函理论（B3LYP-D3/6-31G*）计算淀粉样蛋白模型系统中β-折叠之间的相互作用能，已阐明了芳香族和非芳香族氨基酸在淀粉样蛋白形成中的作用。该模型系统基于两种类型淀粉样蛋白的实验晶体结构：（1）含有芳香族氨基酸的；（2）不含芳香族氨基酸的。数据表明，这两种类型的淀粉样蛋白具有相似的相互作用能，支持了芳香族氨基酸对于淀粉样蛋白形成并非必不可少的实验结果。然而，不同因素对这两种类型淀粉样蛋白的稳定性有贡献。在前者中，芳香族氨基酸的存在显著有助于侧链之间相互作用的强度；芳香族与脂肪族侧链之间的相互作用最强，其次是芳香族-芳香族相互作用，而脂肪族-脂肪族相互作用最弱。在后者中，即不含芳香族残基的淀粉样蛋白，稳定性由脂肪族侧链与主链之间的相互作用以及在某些情况下由氢键提供。
