Theoretical studies in charged biomolecules

在这一应用中，我提出了三个密切相关的项目，概述如下：i)溶液中不对称带电的脂质双层膜的静电学，这项研究的重点将是研究这种膜的构象性质如何受到它们的电荷和介电性质的影响。这项研究的结果直接影响到对红细胞形状变化的预测和对钙诱导的膜融合的潜在影响。(Ii)阳离子多肽不对称结合到带高负电荷的脂膜上。这个项目的目的是研究阳离子多肽与带有相反电荷的脂膜(例如，细菌膜)的不对称结合；这种结合最初是由多肽和阴离子脂类之间的静电吸引，然后是多肽和膜之间的疏水吸引所驱动的。我们将研究不对称结合是如何使膜变形或伸展(并最终破裂)的。(Iii)交替带电的多肽的链内和链间相互作用(和聚集)。交替带电的多肽是那些沿着其骨架交替带正负电荷的多肽，因此能够以依赖于电荷顺序的方式自组装成聚集体。最近，我们研究了模型多肽的自组装(即，我们建议进行分子动力学模拟，以估计相关的时间尺度(例如，链内崩溃和链间碰撞的时间)，并研究它们对多肽自组装的影响。

In this application, I propose three closely-related projects as outlined below:   i) "Electrostatics of asymmetrically-charged lipid-bilayer membranes in solutions, in which one of the layers is more highly charged."  The focus will be on studying how the conformational properties of such membranes are influenced by their charge and dielectric properties.  The outcome of this study has a direct impact on predictions of red-cell shape changes and potential implications for calcium-induced membrane fusion.   ii) "Asymmetrical binding of cationic peptides onto a highly-negatively charged lipid membrane."  This project is aimed at studying asymmetrical binding of cationic peptides onto an oppositely-charged lipid membrane  (e.g., a bacterial membrane), which carries a large fraction of anionic lipids; the binding is initially driven by the electrostatic attraction between the peptide and anionic lipids, and then by the hydrophobic attraction between the peptide and the membrane.  We will investigate how the membrane is deformed or stretched out (and eventually ruptured) by the asymmetrical binding.   iii) "Intra-chain and inter-chain interactions (and aggregation) of alternatively-charged peptides."   Alternatively-charged peptides are those with alternating positive and negative charges along their backbone and thus have the ability to self-assemble into aggregates in a charge-sequence dependent way.  Recently we studied the self-assembly of model peptides (i.e., EAK16s) using Monte Carlo (MC) simulations mostly at a single chain level.  We propose to carry out molecular dynamics simulations to estimate relevant time scales  (e.g., times for intra-chain collapse and inter-chain collision) and to study their consequences on the self-assembly of the peptides.