Activity determinants of helical antimicrobial peptides: a large-scale computational study.
Activity determinants of helical antimicrobial peptides: a large-scale computational study.
复制标题
螺旋抗菌肽的活性决定因素：一项大规模计算研究。
DOI：
10.1371/journal.pone.0066440
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lazaridis T
中科院分区：
文献类型：
--
作者：
He Y;Lazaridis T
抗菌肽（Antimicrobial Peptides，AMP）是由多种微生物产生的一类具有潜在应用价值的新型抗生素。这些肽中的大多数是阳离子的，并且被认为通过使细菌膜透化而起作用，通过制造孔或通过溶解它（“地毯”模型）。文献中的一个关键假设是抗微生物和溶血活性分别与阴离子和两性离子膜的结合亲和力相关。在这里，我们测试这一假设，通过使用从文献中收集的结合自由能数据和理论结合能计算从隐式膜模型为53螺旋AMP。我们确实发现了结合能和生物活性之间的相关性，这取决于膜阴离子含量：抗菌活性与转移到阴离子脂质分数高于30%的膜的能量相关性最好，溶血活性与转移到10%阴离子膜的能量相关性最好。然而，相关性很弱，相关系数高达0.4。还发现生物活性与肽的其他物理描述符的弱相关性，例如表面积占用，其与抗菌活性显著相关;插入深度，其与溶血活性显著相关;和结构波动，其与两种活性显著相关。在MIC下，许多肽的膜表面覆盖率估计远低于“地毯”机制所需的覆盖率。那些在低表面覆盖率下有活性的肽往往是文献中鉴定为成孔的那些。还计算了这些肽从平面膜到圆柱形和环形孔的转移能。在几乎所有的情况下，环形孔的传递能是负的，而圆柱形孔是更有利的中性比阴离子膜。传递到孔隙的能量与“地毯”模型的预测偏差相关。
Antimicrobial peptides (AMPs), produced by a wide range of organisms, have attracted attention due to their potential use as novel antibiotics. The majority of these peptides are cationic and are thought to function by permeabilizing the bacterial membrane, either by making pores or by dissolving it (‘carpet’ model). A key hypothesis in the literature is that antimicrobial and hemolytic activity correlate with binding affinity to anionic and zwitterionic membranes, respectively. Here we test this hypothesis by using binding free energy data collected from the literature and theoretical binding energies calculated from implicit membrane models for 53 helical AMPs. We indeed find a correlation between binding energy and biological activity, depending on membrane anionic content: antibacterial activity correlates best with transfer energy to membranes with anionic lipid fraction higher than 30% and hemolytic activity correlates best with transfer energy to a 10% anionic membrane. However, the correlations are weak, with correlation coefficient up to 0.4. Weak correlations of the biological activities have also been found with other physical descriptors of the peptides, such as surface area occupation, which correlates significantly with antibacterial activity; insertion depth, which correlates significantly with hemolytic activity; and structural fluctuation, which correlates significantly with both activities. The membrane surface coverage by many peptides at the MIC is estimated to be much lower than would be required for the ‘carpet’ mechanism. Those peptides that are active at low surface coverage tend to be those identified in the literature as pore-forming. The transfer energy from planar membrane to cylindrical and toroidal pores was also calculated for these peptides. The transfer energy to toroidal pores is negative in almost all cases while that to cylindrical pores is more favorable in neutral than in anionic membranes. The transfer energy to pores correlates with the deviation from predictions of the ‘carpet’ model.
登录
查看更多内容
影响因子：
2.9
作者：
Gable, Jonathan E.;Schlamadinger, Diana E.;Cogen, Anna L.;Gallo, Richard L.;Kim, Judy E.
通讯作者：
Kim, Judy E.
影响因子：
2.9
作者：
Clark, Kim S.;Svetlovics, James;McKeown, Alesia N.;Huskins, Laura;Almeida, Paulo F.
通讯作者：
Almeida, Paulo F.
影响因子：
3.4
作者：
Ben-Tal, N;Honig, B;Ben-Shaul, A
通讯作者：
Ben-Shaul, A
影响因子：
3.4
作者：
Hall, Benjamin A.;Chetwynd, Alan P.;Sansom, Mark S. P.
通讯作者：
Sansom, Mark S. P.
DOI：
10.1016/0005-2736(88)90202-7
发表时间：
1988-05-24
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GLASER, RW;LEIKIN, SL;SOKIRKO, AI
通讯作者：
SOKIRKO, AI