Constant pH simulations with the coarse-grained MARTINI model - Application to oleic acid aggregates
Constant pH simulations with the coarse-grained MARTINI model - Application to oleic acid aggregates
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DOI：
10.1139/cjc-2013-0010
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发表时间：
2013-09-01
影响因子：
1.1
通讯作者：
Tieleman, D. Peter
中科院分区：
文献类型：
--
作者：
Bennett, W. F. Drew;Chen, Alexander W.;Tieleman, D. Peter
长链脂肪酸是一类重要的生物分子，具有复杂的聚集行为和pH敏感性。油酸的羧基头基是可电离的，在某些聚集态中，pK（a）会向更大的值移动，甚至超过7。虽然实验已经确定了宏观相行为，但我们还没有了解这种复杂行为的分子水平细节。这种详细程度可能需要充分了解脂肪酸在生物学中的作用以及纳米生物技术和工业应用。在这里，我们介绍了使用恒定pH值的分子动力学（MD）模拟与粗粒度的MARTINI模型，并将该方法应用于油酸聚集体和模型脂质双层。通过在不同恒定pH值下运行模拟，我们确定了油酸在不同环境中的滴定曲线和所得pK（a）。粗粒模型预测pK（a）的正位移，从水中的4.8位移到小胶束中的6.5，以及二油酰磷脂酰胆碱（DOPC）双层中的6.6，与实验估计值相似。胶束的大小随着pH的增加而增加，并与去质子化油酸的分数相关。我们表明，这种组合的恒定pH MD和粗粒度的MARTINI模型可以用来模拟pH依赖的表面活性剂相行为。这表明了大量的潜在的新的应用程序的大规模MARTINI模拟在其他生物系统与电离分子。
Long chain fatty acids are biologically important molecules with complex and pH sensitive aggregation behavior. The carboxylic head group of oleic acid is ionizable, with the pK(a) shifting to larger values, even above a value of 7, in certain aggregate states. While experiments have determined the macroscopic phase behavior, we have yet to understand the molecular level details for this complex behavior. This level of detail is likely required to fully appreciate the role of fatty acids in biology and for nanoscale biotechnological and industrial applications. Here, we introduce the use of constant pH molecular dynamics (MD) simulations with the coarse-grained MARTINI model and apply the method to oleic acid aggregates and a model lipid bilayer. By running simulations at different constant pH values, we determined titration curves and the resulting pK(a) for oleic acid in different environments. The coarse-grained model predicts positive pK(a) shifts, with a shift from 4.8 in water to 6.5 in a small micelle, and 6.6 in a dioleoylphosphatidylcholine (DOPC) bilayer, similar to experimental estimates. The size of the micelles increased as the pH increased, and correlated with the fraction of deprotonated oleic acid. We show this combination of constant pH MD and the coarse-grained MARTINI model can be used to model pH-dependent surfactant phase behavior. This suggests a large number of potential new applications of large-scale MARTINI simulations in other biological systems with ionizable molecules.