Department of Chemistry & Biochemistry, University of Oklahoma, Norman, Oklahoma, 73019.
Proteins. 2013 Sep;81(9):1542-55. doi: 10.1002/prot.24302. Epub 2013 Jun 22.
Small-soluble amyloid oligomers are believed to play a significant role in the pathology of amyloid diseases. Recently, the atomic structure of a toxic oligomer formed by an 11 residue and its tandem repeat was found to have an out-off register antiparallel β-strands in the shape of a β-barrel. In the present article we investigate the effect of mutations in the hydrophobic cores on the structure and dynamic of the β-barrels using all atom multiple molecular dynamics simulations with an explicit solvent. Extending previous experiments with molecular dynamics simulations we systematically test how stability and formation of cylindrin depends on the interplay between hydrophobicity and steric effects of the core residues. We find that strong hydrophobic interactions between geometrically fitting residues keep the strands (both in register and out-off-register interface) in close proximity, which in turn stabilizes the side-chain and main-chain hydrogen bonds, and the salt bridges on the outer surface along the weak out-of-register interface. Our simulations also indicate presence of water molecules in the hydrophobic interior of the cylindrin β-barrel.Proteins 2013.
小可溶性淀粉样寡聚物被认为在淀粉样变性疾病的病理学中起重要作用。最近，发现由 11 个残基及其串联重复形成的有毒寡聚物的原子结构具有一种非对齐的反平行 β-折叠，形状为β-桶。在本文中，我们使用含显式溶剂的全原子多分子动力学模拟研究了疏水核突变对β-桶结构和动力学的影响。通过扩展先前的分子动力学模拟实验，我们系统地测试了疏水性和核心残基的空间位阻效应对圆柱蛋白稳定性和形成的影响。我们发现，几何上匹配的残基之间的强疏水相互作用使链（无论是在对齐还是非对齐界面上）保持接近，这反过来又稳定了侧链和主链氢键，以及在弱非对齐界面上的盐桥。我们的模拟还表明，水分子存在于圆柱蛋白β-桶的疏水内部。蛋白质 2013 年。
