Center for Simulational Physics, The University of Georgia, Athens, Georgia 30602-0002, USA.
Scientific IT Services, ETH Zurich, 8092 Zurich, Switzerland.
J Chem Phys. 2018 Oct 28;149(16):164913. doi: 10.1063/1.5026256.
We studied the folding behavior of two coarse-grained, lattice models, the HP (hydrophobic-polar) model and the semi-flexible H0P model, whose 124 monomer long sequences were derived from the protein Ribonuclease A. Taking advantage of advanced parallel computing techniques, we applied replica exchange Wang-Landau sampling and calculated the density of states over the models entire energy ranges to high accuracy. We then determined both energetic and structural quantities in order to elucidate the folding behavior of each model completely. As a result of sufficiently long sequences and model complexity, yet computational accessibility, we were able to depict distinct free energy folding funnels for both models. In particular, we found that the HP model folds in a single-step process with a very highly degenerate native state and relatively flat low temperature folding funnel minimum. By contrast, the semi-flexible H0P model folds via a multi-step process and the native state is almost four orders of magnitude less degenerate than that for the HP model. In addition, for the H0P model, the bottom of the free energy folding funnel remains rough, even at low temperatures.
我们研究了两种粗粒化的格子模型的折叠行为，即 HP（疏水-极性）模型和半柔性 H0P 模型，它们的 124 个单体长序列来源于蛋白质核糖核酸酶 A。利用先进的并行计算技术，我们应用 replica exchange Wang-Landau 采样（replica exchange Wang-Landau sampling）并计算了模型整个能量范围内的态密度（state density），以达到高精度。然后，我们确定了能量和结构两个方面的量，以便完全阐明每个模型的折叠行为。由于序列足够长且模型复杂，但计算上可访问性，我们能够为这两个模型描绘出明显的自由能折叠漏斗（free energy folding funnel）。特别是，我们发现 HP 模型以单步过程折叠，具有非常高度简并的天然状态和相对平坦的低温折叠漏斗最小值。相比之下，半柔性 H0P 模型通过多步过程折叠，天然状态的简并度几乎比 HP 模型低四个数量级。此外，对于 H0P 模型，即使在低温下，自由能折叠漏斗的底部仍然很粗糙。
