School of Physics, University College Dublin, Belfield, Dublin 4, Ireland.
Biophys Chem. 2012 Jun;167:1-7. doi: 10.1016/j.bpc.2012.03.010. Epub 2012 Apr 5.
We study the conformational dynamics of the human Islet Amyloid Polypeptide (hIAPP) molecule - a 37 residue-long peptide associated to type 2 diabetes - using molecular dynamics (MD) simulations. We identify partially structured conformational states of the hIAPP monomer, categorized by both end-to-end distance and secondary structure, as suggested by previous experimental and computational studies. The MD trajectories of hIAPP are analyzed using data-driven methods, in particular principal component analysis, in order to identify preferred conformational states of the amylin monomer and to discuss their relative stability as compared to corresponding states in the amylin dimer. These potential hIAPP conformational states could be further tested and described experimentally, or in conjunction with modern computational analysis tools such as Markov state-based methods for extracting kinetics and thermodynamics from atomistic MD trajectories.
我们使用分子动力学（MD）模拟研究了与 2 型糖尿病相关的 37 个残基长肽——人胰岛淀粉样多肽（hIAPP）分子的构象动力学。我们根据之前的实验和计算研究，通过末端到末端的距离和二级结构，确定了 hIAPP 单体的部分结构化构象状态。使用数据驱动的方法（特别是主成分分析）分析 hIAPP 的 MD 轨迹，以确定淀粉样肽单体的首选构象状态，并讨论它们相对于淀粉样肽二聚体中相应状态的相对稳定性。这些潜在的 hIAPP 构象状态可以进一步通过实验进行测试和描述，或者与现代计算分析工具（如基于马尔可夫状态的方法）结合使用，从原子 MD 轨迹中提取动力学和热力学信息。
