The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions: a replica exchange molecular dynamics study
The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions: a replica exchange molecular dynamics study
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中性和低pH条件下朊病毒蛋白螺旋片段的内在螺旋倾向：复制品交换分子动力学研究
DOI：
10.1007/s00894-013-1985-7
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发表时间：
2013-11-01
影响因子：
2.2
通讯作者：
Mei, Ye
中科院分区：
文献类型：
--
作者：
Lu, Xiaoliang;Zeng, Juan;Mei, Ye
在中性和酸性水溶液中的双交换分子动力学模拟研究了叙利亚仓鼠（syPrP）和人类（huPrP）朊病毒蛋白中三个螺旋的内在螺旋倾向。syPrP HA和huPrP HA的螺旋倾向在两种pH条件下都非常高，这意味着HA几乎不参与螺旋向β的转变。SyPrP HB链具有较强的延伸构象倾向，这可能与Syrian仓鼠感染性朊病毒病的发病机制有关。与huPrP HA和huPrP HB相比，HuPrP HC更倾向于伸展构象，这使得推测它更可能是人朊蛋白富含β结构的来源。我们还注意到盐桥的存在与螺旋倾向无关，表明盐桥不稳定螺旋。
Replica exchange molecular dynamics simulations in neutral and acidic aqueous solutions were employed to study the intrinsic helical propensities of three helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The helical propensities of syPrP HA and huPrP HA are very high under both pH conditions, which implies that HA is barely involved in the helix-to-β transition. The SyPrP HB chain has a strong tendency to adopt an extended conformation, which is possibly involved in the mechanism of infectious prion diseases in Syrian hamster. HuPrP HC has more of a preference for the extended conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it is more likely to be the source of β-rich structure for human prion protein. We also noticed that the presence of salt bridges is not correlated with helical propensity, indicating that salt bridges do not stabilize helices.