School of Systems Biology, George Mason University, Manassas, Virginia 20110, USA.
J Chem Phys. 2011 Jul 21;135(3):035103. doi: 10.1063/1.3610427.
The effect of random reshuffling of amino acids on the properties of dimers formed by Aβ peptides is studied using replica exchange molecular dynamics and united atom implicit solvent model. We show that thermodynamics of dimer assembly and the dimer globule-like state are not affected by sequence permutation. Furthermore, sequence reshuffling does not change the distributions of non-local interactions and, to a large extent, amino acids in the dimer volume. To rationalize these results, we demonstrate that Gaussian statistics applies surprisingly well to the end-to-end distances of the peptides in the dimer implying that non-bonded interactions between distant along the chain amino acids are effectively screened. This observation suggests that peptides in the dimer behave as ideal chains in polymer melt, in which amino acids lose their "identity" and therefore the memory of sequence position. As a result large-scale properties of the dimer become universal or sequence independent. Comparison of our simulations with the prior theoretical studies and their implications for experiments are discussed.
使用 replica exchange 分子动力学和联合原子隐式溶剂模型研究了氨基酸随机重排对 Aβ 肽形成的二聚体性质的影响。我们表明，二聚体组装的热力学和二聚体类球状态不受序列排列的影响。此外，序列重排不会改变非局部相互作用的分布，并且在很大程度上不会改变二聚体体积中氨基酸的分布。为了合理化这些结果，我们证明高斯统计出乎意料地适用于二聚体中肽的末端到末端距离，这意味着沿链的远距离氨基酸之间的非键相互作用被有效屏蔽。这一观察结果表明，二聚体中的肽在聚合物熔体中表现为理想链，其中氨基酸失去了它们的“身份”，因此失去了序列位置的记忆。结果，二聚体的大规模性质变得具有普遍性或与序列无关。讨论了我们的模拟与先前的理论研究的比较及其对实验的影响。
