Mazarakos Konstantinos, Prasad Ramesh, Zhou Huan-Xiang
Department of Physics, University of Illinois at Chicago, Chicago, IL, United States.
Department of Chemistry, University of Illinois at Chicago, Chicago, IL, United States.
Front Mol Biosci. 2022 Oct 24;9:1021939. doi: 10.3389/fmolb.2022.1021939. eCollection 2022.
Phase separation of intrinsically disordered proteins (IDPs) is a phenomenon associated with many essential cellular processes, but a robust method to compute the binodal from molecular dynamics simulations of IDPs modeled at the all-atom level in explicit solvent is still elusive, due to the difficulty in preparing a suitable initial dense configuration and in achieving phase equilibration. Here we present SpiDec as such a method, based on spontaneous phase separation spinodal decomposition that produces a dense slab when the system is initiated at a homogeneous, low density. After illustrating the method on four model systems, we apply SpiDec to a tetrapeptide modeled at the all-atom level and solvated in TIP3P water. The concentrations in the dense and dilute phases agree qualitatively with experimental results and point to binodals as a sensitive property for force-field parameterization. SpiDec may prove useful for the accurate determination of the phase equilibrium of IDPs.
内在无序蛋白质（IDP）的相分离是一种与许多重要细胞过程相关的现象，但是由于难以制备合适的初始致密构型以及实现相平衡，因此仍然难以找到一种强大的方法，从在明确溶剂中全原子水平建模的IDP分子动力学模拟中计算双节线。在此，我们提出了SpiDec这种方法，它基于自发相分离的旋节线分解，当系统从均匀的低密度开始时会产生一个致密平板。在四个模型系统上说明了该方法之后，我们将SpiDec应用于在全原子水平建模并溶解在TIP3P水中的四肽。浓相和稀相中的浓度与实验结果定性一致，并表明双节线是力场参数化的敏感属性。SpiDec可能被证明对准确确定IDP的相平衡有用。
