Department of Cellular and Molecular Biology, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
J Biomol Struct Dyn. 2010 Feb;27(4):551-60. doi: 10.1080/07391102.2010.10507338.
To study structure-activity relationship of antimicrobial peptides and to design novel antimicrobial peptides with selectivity for bacterial cells, we have performed molecular dynamics simulations of the interaction of Piscidin (Pis1) and its two analogues (Pis1-AA and Pis1-PG) with dipalmitoylphosphatidylcholine (DPPC) bilayer through 45 ns. Our results inform us of the detailed location and orientation of the peptide with respect to the bilayer as well as provide about hydrogen-bond-formation patterns and electrostatics interactions. Simulations show that Pis1 and Pis-AA form the most hydrogen bonds and Pis-PG forms the fewest hydrogen bonds with lipid. Thus, Pis1 and Pis-AA should have stronger interactions with the lipid head group when compared to Pis-PG. Experimental studies have shown that Pis1 and Pis1-AA have a high antimicrobial and hemolytic activities, and Pis1-PG has low hemolytic activity while keeps potent antimicrobial activity. Our results complement the previous experimental studies. According to our MD results and previous experimental studies, Pis1 and Pis1-AA are more effective at the zwitterionic bilayer comparing Pis1-PG. These properties of Pis1-PG could be accordance with its low hemolytic activities.
为了研究抗菌肽的结构-活性关系并设计对细菌细胞具有选择性的新型抗菌肽，我们对 Piscidin (Pis1) 及其两种类似物 (Pis1-AA 和 Pis1-PG) 与二棕榈酰磷脂酰胆碱 (DPPC) 双层的相互作用进行了 45 ns 的分子动力学模拟。我们的结果提供了有关肽相对于双层的详细位置和取向的信息，并提供了有关氢键形成模式和静电相互作用的信息。模拟表明，Pis1 和 Pis-AA 与脂质形成的氢键最多，而 Pis-PG 与脂质形成的氢键最少。因此，与 Pis-PG 相比，Pis1 和 Pis-AA 与脂质头部基团的相互作用应该更强。实验研究表明，Pis1 和 Pis1-AA 具有很高的抗菌和溶血活性，而 Pis1-PG 具有较低的溶血活性，但仍保持很强的抗菌活性。我们的结果补充了以前的实验研究。根据我们的 MD 结果和以前的实验研究，与 Pis1-PG 相比，Pis1 和 Pis1-AA 在两性离子双层中更有效。Pis1-PG 的这些特性可能与其较低的溶血活性一致。
