Department of Materials Science and Engineering , North Carolina State University , 911 Partners Way , Raleigh , North Carolina 27695 , United States.
Department of Biomedical Engineering , Duke University , P.O. Box 90281, Durham , North Carolina 27708 , United States.
Biomacromolecules. 2018 Jul 9;19(7):2496-2505. doi: 10.1021/acs.biomac.8b00099. Epub 2018 Apr 30.
Elastin-like polypeptides (ELP) exhibit an inverse temperature transition or lower critical solution temperature (LCST) transition phase behavior in aqueous solutions. In this paper, the thermal responsive properties of the canonical ELP, poly(VPGVG), and its reverse sequence poly(VGPVG) were investigated by turbidity measurements of the cloud point behavior, circular dichroism (CD) measurements, and all-atom molecular dynamics (MD) simulations to gain a molecular understanding of mechanism that controls hysteretic phase behavior. It was shown experimentally that both poly(VPGVG) and poly(VGPVG) undergo a transition from soluble to insoluble in aqueous solution upon heating above the transition temperature ( T). However, poly(VPGVG) resolubilizes upon cooling below its T, whereas the reverse sequence, poly(VGPVG), remains aggregated despite significant undercooling below the T. The results from MD simulations indicated that a change in sequence order results in significant differences in the dynamics of the specific residues, especially valines, which lead to extensive changes in the conformations of VPGVG and VGPVG pentamers and, consequently, dissimilar propensities for secondary structure formation and overall structure of polypeptides. These changes affected the relative hydrophilicities of polypeptides above T, where poly(VGPVG) is more hydrophilic than poly(VPGVG) with more extended conformation and larger surface area, which led to formation of strong interchain hydrogen bonds responsible for stabilization of the aggregated phase and the observed thermal hysteresis for poly(VGPVG).
弹性蛋白样多肽（ELP）在水溶液中表现出逆温转变或低临界溶液温度（LCST）转变的相行为。在本文中，通过浊度测量法研究了典型的 ELP 聚（VPGVG）及其反向序列聚（VGPVG）的热响应特性，圆二色性（CD）测量和全原子分子动力学（MD）模拟，以获得控制滞后相行为的机制的分子理解。实验表明，聚（VPGVG）和聚（VGPVG）在加热到转变温度（T）以上时都会从水溶液中可溶性转变为不溶性。然而，聚（VPGVG）在冷却到 T 以下时会重新溶解，而反向序列聚（VGPVG）尽管在 T 以下有明显的过冷，但仍保持聚集状态。MD 模拟结果表明，序列顺序的变化会导致特定残基的动力学发生显著差异，特别是缬氨酸，这导致 VPGVG 和 VGPVG 五聚体的构象发生广泛变化，从而导致二级结构形成和多肽整体结构的不同倾向。这些变化影响了 T 以上多肽的相对亲水性，其中聚（VGPVG）比聚（VPGVG）更亲水，具有更伸展的构象和更大的表面积，这导致形成强链间氢键，负责稳定聚集相和观察到的聚（VGPVG）的热滞后。
