Early stages in Ab1-42 spontaneous aggregation: an unbiased dataset from coarse-grained molecular dynamics simulations.

Soluble oligomers of Aβ-1-42 are widely recognized as crucial targets for the design of inhibitors for potential therapeutic intervention against Alzheimer´s disease. However, the intrinsically disordered character of this polypeptide poses serious difficulties for the experimental determination of conserved structural motifs. Indeed, initial aggregation steps are extremely challenging for state-of-the-art experimental techniques. Although molecular dynamics simulations harbor the potential to capture such initial association events, unbiased exploration of the conformational landscape available to unstructured dimers implies a significant computational cost.
Here, we provide a dataset of configurations of Aβ1-42 dimers obtained by coarse-grained molecular dynamics (MD) simulations using the SIRAH force field. Trajectories are provided in standard gromacs format and can be easily converted to fully atomistic representations for visualization and analysis using molecular visualization/analysis software. The dataset contains MD trajectories of Aβ1-42 that undergo spontaneous and unbiased dimerization. We provide the time series of 25 replicates simulated for 10 microseconds under room conditions and physiological salt concentration. These multiple aggregation events provide valuable information not only on new binding pockets formed by the dimeric interface but also monomeric hot spots that can be targeted by small molecules on high-throughput docking campaigns. Alternatively, Aβ1-42 dimers could be used as aggregation seeds in studies of Aβ secondary nucleation.

可溶性Aβ₁₋₄₂寡聚体已被广泛认为是设计阿尔茨海默病（Alzheimer's disease）治疗性抑制剂的关键靶点。然而，该多肽的内在无序特性给保守结构基序的实验测定带来了极大困难。事实上，初始聚集过程对当前最先进的实验技术而言仍极具挑战性。尽管分子动力学（MD）模拟有望捕捉这类初始聚集事件，但对无结构二聚体的构象空间进行无偏探索，往往需要付出高昂的计算成本。
本数据集提供了使用SIRAH力场开展粗粒度分子动力学（MD）模拟得到的Aβ₁₋₄₂二聚体构型数据。轨迹文件采用标准GROMACS格式存储，可通过分子可视化与分析软件便捷转换为全原子构型，用于后续可视化与分析。数据集包含发生自发且无偏二聚化过程的Aβ₁₋₄₂分子动力学轨迹：我们模拟了25次重复实验，每次时长10微秒，模拟环境为室温条件与生理盐浓度。这些多组聚集事件不仅能为二聚体界面形成的新型结合口袋提供有价值的信息，还能识别可用于小分子高通量对接研究的单体热点区域。此外，Aβ₁₋₄₂二聚体还可作为聚集种子，用于Aβ的次级成核相关研究。