Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics Simulations

详细信息    查看全文

• 作者：Chenyi Liao ; Myvizhi Esai Selvan ; Jun Zhao ; Jonathan L. Slimovitch ; Severin T. Schneebeli ; Mee Shelley ; John C. Shelley ; Jianing Li
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：August 20, 2015
• 年：2015
• 卷：119
• 期：33
• 页码：10390-10398
• 全文大小：594K
• ISSN：1520-5207

文摘

Melittin is a natural peptide that aggregates in aqueous solutions with paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is known about the molecular mechanisms of melittin aggregation in solution, we simulated its self-aggregation process under various conditions. After confirming the stability of a melittin tetramer in solution, we observed鈥攆or the first time in atomistic detail鈥攖hat four separated melittin monomers aggregate into a tetramer. Our simulated dependence of melittin aggregation on peptide concentration, temperature, and ionic strength is in good agreement with prior experiments. We propose that melittin mainly self-aggregates via a mechanism involving the sequential addition of monomers, which is supported by both qualitative and quantitative evidence obtained from unbiased and metadynamics simulations. Moreover, by combining computer simulations and a theory of the electrical double layer, we provide evidence to suggest why melittin aggregation in solution likely stops at the tetramer, rather than forming higher-order oligomers. Overall, our study not only explains prior experimental results at the molecular level but also provides quantitative mechanistic information that may guide the engineering of melittin for higher efficacy and safety.