Musiani F, Giorgetti A
Laboratory of Bioinorganic Chemistry, University of Bologna, Bologna, Italy.
Applied Bioinformatics Group, University of Verona, Verona, Italy.
Int Rev Cell Mol Biol. 2017;329:49-77. doi: 10.1016/bs.ircmb.2016.08.009. Epub 2016 Oct 22.
Cells are extremely crowded environments, thus the use of diluted salted aqueous solutions containing a single protein is too simplistic to mimic the real situation. Macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, interactions with cognate biomolecules, and pathological aggregation. The latter phenomenon typically leads to the formation of amyloid fibrils that are linked to several lethal neurodegenerative diseases, but that can also play a functional role in certain organisms. The majority of molecular simulations performed before the last few years were conducted in diluted solutions and were restricted both in the timescales and in the system dimensions by the available computational resources. In recent years, several computational solutions were developed to get close to physiological conditions. In this review we summarize the main computational techniques used to tackle the issue of protein aggregation both in a diluted and in a crowded environment.
细胞是极其拥挤的环境，因此使用含有单一蛋白质的稀释盐水溶液来模拟真实情况过于简单。大分子拥挤可能会影响蛋白质结构、折叠、形状、构象稳定性、小分子结合、酶活性、与同源生物分子的相互作用以及病理性聚集。后一种现象通常会导致淀粉样纤维的形成，这与几种致命的神经退行性疾病有关，但在某些生物体中也可能发挥功能作用。在过去几年之前进行的大多数分子模拟都是在稀释溶液中进行的，并且在时间尺度和系统维度上都受到可用计算资源的限制。近年来，人们开发了几种计算方法以接近生理条件。在这篇综述中，我们总结了用于解决稀释和拥挤环境中蛋白质聚集问题的主要计算技术。
