We have computed the low energy minima for the two endomorphin peptides, N-acetyl-Tyr-Pro-Trp-Phe-NHCH₃ (endomorphin 1) and Tyr-Pro-Phe-Phe-NHCH₃ (endomorphin 2) in aqueous solution. These peptides block pain without inducing the harmful side effects of the opiates that bind to the same mu opiate receptor but have short half lives. From over 1000 starting conformations for each peptide, we find less than 200 low energy structures whose conformational energies were ≤ 5 kcal/mole of the energy of the global minimum. The most probable conformations calculated using the Boltzmann distribution for both peptides were similar to one another. Using the letter representation for backbone conformational states, these most probable structures were D A E E for endomorphin 1 and E A E E for endomorphin 2. Both of these structures form reverse turns at Pro 2-Trp (Phe) 3 resulting in the juxtaposition of the aromatic rings of Tyr 1 and Phe 4. The Trp residue of endomorphin 1 points to the back of the reverse turn. These features may be useful in the design of non-peptide analogues that will have longer half-lives than the peptides.

中文翻译：

---

内源性Mu受体特异性肽的低能构象。

我们已经计算出两种内啡肽肽（N-乙酰基-Tyr-Pro-Trp-Phe-NHCH ₃（内啡肽1）和Tyr-Pro-Phe-Phe-NHCH ₃）的低能极小值（内啡肽2）在水溶液中。这些肽可阻止疼痛，而不会诱导与相同的阿片受体结合的阿片的有害副作用，但半衰期短。从每种肽的1000多个起始构象中，我们发现不到200个低能结构，其构象能量≤全局最小能量的5 kcal / mole。使用玻尔兹曼分布计算的两种肽的最可能构象彼此相似。用字母表示骨架构象状态，这些最可能的结构是内啡肽1的DAEE和内啡肽2的EAEE。这两个结构在Pro 2-Trp（Phe）3处形成反向转角，导致Tyr芳香环并置1和Phe 4。内啡肽1的Trp残基指向反向转弯的后面。这些特征可用于设计比肽具有更长的半衰期的非肽类似物。