Sayyed-Ahmad Abdallah, Kaznessis Yiannis N
Department of Chemical Engineering and Materials Science and the Digital Technology Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS One. 2009;4(3):e4799. doi: 10.1371/journal.pone.0004799. Epub 2009 Mar 11.
Continuum models that describe the effects of solvent and biological membrane molecules on the structure and behavior of antimicrobial peptides, holds a promise to improve our understanding of the mechanisms of antimicrobial action of these peptides. In such methods, a lipid bilayer model membrane is implicitly represented by multiple layers of relatively low dielectric constant embedded in a high dielectric aqueous solvent, while an antimicrobial peptide is accounted for by a dielectric cavity with fixed partial charge at the center of each one of its atoms. In the present work, we investigate the ability of continuum approaches to predict the most probable orientation of the beta-hairpin antimicrobial peptide Protegrin-1 (PG-1) in DLPC lipid bilayers by calculating the difference in the transfer free energy from an aqueous environment to a membrane-water environment for multiple orientations. The transfer free energy is computed as a sum of two terms; polar/electrostatic and non-polar. They both include energetic and entropic contributions to the free energy. We numerically solve the Poisson-Boltzmann equation to calculate the electrostatic contribution to the transfer free energy, while the non-polar contribution to the free energy is approximated using a linear solvent accessible surface area relationships. The most probable orientation of PG-1 is that with the lowest relative transfer free energy. Our simulation results indicate that PG-1 assumes an oblique orientation in DLPC lipid bilayers. The predicted most favorable orientation was with a tilt angle of 19 degrees, which is in qualitative agreement with the experimentally observed orientations derived from solid-state NMR data.
描述溶剂和生物膜分子对抗菌肽结构和行为影响的连续介质模型，有望增进我们对这些肽抗菌作用机制的理解。在这类方法中，脂质双层模型膜由嵌入高介电常数水性溶剂中的多层相对低介电常数物质隐式表示，而抗菌肽则由位于其每个原子中心具有固定部分电荷的介电腔来描述。在本工作中，我们通过计算多种取向从水环境到膜 - 水环境的转移自由能差异，研究连续介质方法预测β - 发夹抗菌肽Protegrin - 1（PG - 1）在DLPC脂质双层中最可能取向的能力。转移自由能计算为两项之和；极性/静电项和非极性项。它们都包括对自由能的能量和熵贡献。我们通过数值求解泊松 - 玻尔兹曼方程来计算转移自由能的静电贡献，而自由能的非极性贡献则使用线性溶剂可及表面积关系进行近似。PG - 1最可能的取向是具有最低相对转移自由能的取向。我们的模拟结果表明，PG - 1在DLPC脂质双层中呈倾斜取向。预测的最有利取向倾斜角为19度，这与从固态NMR数据得出的实验观察取向在定性上一致。
