Resolution exchange with tunneling for enhanced sampling of protein landscapes.
Resolution exchange with tunneling for enhanced sampling of protein landscapes.
复制标题
分辨率与隧道交换，以增强蛋白质景观的采样。
DOI：
10.1103/physreve.106.015302
复制
发表时间：
2022-07
影响因子：
2.4
通讯作者：
Hansmann, Ulrich H. E.
中科院分区：
文献类型：
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作者：
Yasar, Fatih;Ray, Alan J.;Hansmann, Ulrich H. E.
蛋白质折叠和蛋白质缔合的模拟发生在比全原子分子动力学模拟通常所涵盖的大几个数量级的时间尺度上。使用低分辨率模型可以解决这个问题，但可能会降低模拟的准确性。我们引入了一种基于复制交换的多尺度采样技术，该技术将粗粒度模拟中的更快采样与全原子模拟的潜在更高精度相结合。在测试了我们的Tunnel分辨率交换（ResET）在Trp笼蛋白模拟中的效率后，我们使用我们的方法比较野生型和A2 T突变Aβ1-42肽的景观，Trp笼蛋白是一种经常用于评估蛋白质模拟中采样技术的模型。我们的研究结果表明，一个小的疏水性丙氨酸（A）突变为一个大的极性苏氨酸（T）可能会干扰Aβ-纤维的自组装机制。
Simulations of protein folding and protein association happen on timescales that are orders of magnitude larger than what can typically be covered in all-atom molecular dynamics simulations. Use of low-resolution models alleviates this problem but may reduce the accuracy of the simulations. We introduce a replica-exchange-based multiscale sampling technique that combines the faster sampling in coarse-grained simulations with the potentially higher accuracy of all-atom simulations. After testing the efficiency of our Resolution Exchange with Tunneling (ResET) in simulations of the Trp-cage protein, an often used model to evaluate sampling techniques in protein simulations, we use our approach to compare the landscape of wild type and A2T mutant Aβ1–42 peptides. Our results suggest a mechanism by that the mutation of a small hydrophobic Alanine (A) into a bulky polar Threonine (T) may interfere with the self-assembly of Aβ-fibrils.