Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2022 Jun 20;27(12):3936. doi: 10.3390/molecules27123936.
Despite the enormous efforts made to develop other fusion inhibitors for HIV, the enfuvirtide (known as T20) peptide is the only approved HIV-1 inhibitory drug so far. Investigating the role of potential residues of the T20 peptide's conformational dynamics could help us to understand the role of potential residues of the T20 peptide. We investigated T20 peptide conformation and binding interactions with the HIV-1 receptor (i.e., gp41) using MD simulations and docking techniques, respectively. Although the mutation of E143 into alanine decreased the flexibility of the E143A mutant, the conformational compactness of the mutant was increased. This suggests a potential role of E143 in the T20 peptide's conformation. Interestingly, the free energy landscape showed a significant change in the wild-type T20 minimum, as the E143A mutant produced two observed minima. Finally, the docking results of T20 to the gp41 receptor showed a different binding interaction in comparison to the E143A mutant. This suggests that E143 residue can influence the binding interaction with the gp41 receptor. Overall, the E143 residue showed a significant role in conformation and binding to the HIV-1 receptor. These findings can be helpful in optimizing and developing HIV-1 inhibitor peptides.
尽管为开发其他 HIV 融合抑制剂做出了巨大努力，但恩夫韦肽（也称为 T20）肽仍然是迄今为止唯一获得批准的 HIV-1 抑制药物。研究 T20 肽构象动力学的潜在残基的作用可以帮助我们了解 T20 肽的潜在残基的作用。我们分别使用 MD 模拟和对接技术研究了 T20 肽构象和与 HIV-1 受体（即 gp41）的结合相互作用。尽管将 E143 突变为丙氨酸降低了 E143A 突变体的灵活性，但突变体的构象紧凑性增加。这表明 E143 在 T20 肽构象中可能具有作用。有趣的是，自由能景观显示野生型 T20 最小值发生了显著变化，因为 E143A 突变体产生了两个观察到的最小值。最后，T20 与 gp41 受体的对接结果显示与 E143A 突变体相比，结合相互作用不同。这表明 E143 残基可以影响与 gp41 受体的结合相互作用。总体而言，E143 残基在构象和与 HIV-1 受体的结合中表现出重要作用。这些发现有助于优化和开发 HIV-1 抑制剂肽。
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