Molecular Biotechnology, Turkish-German University, Istanbul, Turkey.
Department of Molecular Medicine, USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Chem Biol Drug Des. 2021 May;97(5):1100-1108. doi: 10.1111/cbdd.13830. Epub 2021 Feb 22.
Our recent studies revealed that none of the selected widely used force field parameters and molecular dynamics simulation techniques yield structural properties for the intrinsically disordered α-synuclein that are in agreement with various experiments via testing different force field parameters. Here, we extend our studies on the secondary structure properties of the disordered amyloid-β(1-40) peptide in aqueous solution. For these purposes, we conducted extensive replica exchange molecular dynamics simulations and obtained extensive molecular dynamics simulation trajectories from David E. Shaw group. Specifically, these molecular dynamics simulations were conducted using various force field parameters and obtained results are compared to our replica exchange molecular dynamics simulations and experiments. In this study, we calculated the secondary structure abundances and radius of gyration values for amyloid-β(1-40) that were simulated using varying force field parameter sets and different simulation techniques. In addition, the intrinsic disorder propensity, as well as sequence-based secondary structure predisposition of amyloid-β(1-40) and compared the findings with the results obtained from molecular simulations using various force field parameters and different simulation techniques. Our studies clearly show that the epitope region identification of amyloid-β(1-40) depends on the chosen simulation technique and chosen force field parameters. Based on comparison with experiments, we find that best computational results in agreement with experiments are obtained using the a99sb*-ildn, charmm36m, and a99sb-disp parameters for the amyloid-β(1-40) peptide in molecular dynamics simulations without parallel tempering or via replica exchange molecular dynamics simulations.
我们最近的研究表明，通过测试不同的力场参数，在所选择的广泛使用的力场参数和分子动力学模拟技术中，没有一种方法可以得出与各种实验一致的天然无序α-突触核蛋白的结构特性。在这里，我们扩展了我们对无序淀粉样β（1-40）肽在水溶液中二级结构性质的研究。为此，我们进行了广泛的 replica 交换分子动力学模拟，并从 David E. Shaw 小组获得了广泛的分子动力学模拟轨迹。具体来说，这些分子动力学模拟使用了各种力场参数，并将获得的结果与我们的 replica 交换分子动力学模拟和实验进行了比较。在这项研究中，我们计算了使用不同力场参数集和不同模拟技术模拟的淀粉样β（1-40）的二级结构丰度和回转半径值。此外，我们还计算了淀粉样β（1-40）的固有无序倾向以及基于序列的二级结构倾向，并将这些发现与使用各种力场参数和不同模拟技术进行分子模拟获得的结果进行了比较。我们的研究清楚地表明，淀粉样β（1-40）的表位区域识别取决于所选择的模拟技术和所选择的力场参数。通过与实验进行比较，我们发现，在没有平行温度或通过 replica 交换分子动力学模拟的情况下，使用 a99sb*-ildn、charmm36m 和 a99sb-disp 对淀粉样β（1-40）肽进行分子动力学模拟，可获得与实验最吻合的最佳计算结果。
