Department of Physics, Hiram College, Hiram, Ohio 44234, USA.
J Chem Phys. 2020 Nov 7;153(17):174901. doi: 10.1063/5.0025640.
A flexible polymer chain in the presence of inert macromolecular crowders will experience a loss of configurational entropy due to the crowder excluded volume. This entropy reduction will be most pronounced in good solvent conditions where the chain assumes an expanded coil conformation. For polymers that undergo a folding transition from a coil to a compact ordered state, as is the case for many globular proteins, macromolecular crowding is expected to stabilize the folded state and thereby shift the transition location. Here, we study such entropic stabilization effects for a tangent square-well sphere chain (monomer diameter σ) in the presence of hard-sphere (HS) crowders (diameter D ≥ σ). We use the Wang-Landau simulation algorithm to construct the density of states for this chain in a crowded environment and are thus able to directly compute the reduction in configurational entropy due to crowding. We study both a chain that undergoes all-or-none folding directly from the coil state and a chain that folds via a collapsed-globule intermediate state. In each case, we find an increase in entropic stabilization for the compact states with an increase in crowder density and, for fixed crowder density, with a decrease in crowder size (concentrated, small crowders have the largest effect). The crowder significantly reduces the average size for the unfolded states while having a minimal effect on the size of the folded states. In the athermal limit, our results directly provide the confinement free energy due to crowding for a HS chain in a HS solvent.
在惰性大分子拥挤物存在的情况下，柔性聚合物链由于拥挤物的排除体积，将经历构象熵的损失。这种熵的减少在良溶剂条件下最为明显，在这种条件下，链呈现出扩展的线圈构象。对于那些经历从线圈到紧凑有序状态的折叠转变的聚合物，就像许多球状蛋白质一样，大分子拥挤被预期会稳定折叠状态，从而改变转变位置。在这里，我们研究了在硬球（HS）拥挤物（直径 D ≥ σ）存在下，切线方阱球链（单体直径 σ）中的这种熵稳定化效应。我们使用 Wang-Landau 模拟算法在拥挤环境中构建了这个链的态密度，从而能够直接计算由于拥挤而导致的构象熵的减少。我们研究了直接从线圈状态经历全或无折叠的链和通过折叠中间态的链。在每种情况下，我们都发现随着拥挤物密度的增加，紧凑态的熵稳定性增加，并且对于固定的拥挤物密度，随着拥挤物尺寸的减小（浓缩的、小的拥挤物具有最大的效果），熵稳定性增加。拥挤物显著减小了未折叠状态的平均尺寸，而对折叠状态的尺寸影响最小。在非热极限下，我们的结果直接提供了在 HS 溶剂中 HS 链由于拥挤而产生的限制自由能。
