The interconversion between the left- and right-handed helical folds of a polypeptide defines a dual-funneled free energy landscape. In this context, the funnel minima are connected through a continuum of unfolded conformations, evocative of the classical helix-coil transition. Physical intuition and recent conjectures suggest that this landscape can be mapped by assigning a left- or right-handed helical state to each residue. We explore this possibility using all-atom replica exchange molecular dynamics and an Ising-like model, demonstrating that the energy landscape architecture is at odds with a two-state picture. A three-state model—left, right, and unstructured—can account for most key intermediates during chiral interconversion. Competing folds and excited conformational states still impose limitations on the scope of this approach. However, the improvement is stark: Moving from a two-state to a three-state model decreases the fit error from 1.6 k_BT to 0.3 k_BT along the left-to-right interconversion pathway.

中文翻译：

---

双漏斗能源景观的 spin-1 表示


多肽的左旋和右旋螺旋折叠之间的相互转换定义了双漏斗自由能景观。在这种情况下，漏斗最小值通过连续的展开构象连接起来，让人想起经典的螺旋-螺旋过渡。物理直觉和最近的猜想表明，可以通过为每个残基分配左手或右手螺旋状态来绘制这种景观。我们使用全原子复制品交换分子动力学和类伊辛模型探索这种可能性，证明能量景观结构与两种状态的图景不一致。三态模型（左、右和非结构化）可以解释手性互变过程中的大多数关键中间体。竞争折叠和激发构象状态仍然限制了这种方法的范围。然而，改进是显而易见的：从二态模型转变为三态模型，沿着从左到右的相互转换路径，拟合误差从 1.6 k _B T降低到 0.3 k _B T。