Theoretical studies in charged biomolecules

在本申请中，我提出了三个密切相关的项目，如下所述： i）“溶液中不对称带电脂质双层膜的静电，其中一层带电更高。“重点将是研究这种膜的构象特性如何受到其电荷和介电特性的影响。 这项研究的结果对红细胞形状变化的预测和钙诱导的膜融合的潜在影响有直接影响。 ii）“阳离子肽与高负电荷脂质膜的不对称结合。“该项目旨在研究阳离子肽与带相反电荷的脂质膜（例如，细菌膜），其携带大部分阴离子脂质;结合最初由肽和阴离子脂质之间的静电吸引力驱动，然后由肽和膜之间的疏水吸引力驱动。 我们将研究膜是如何变形或拉伸（并最终破裂）的不对称结合。 iii）“交替带电肽的链内和链间相互作用（和聚集）。" 带交替电荷的肽是沿其主链具有交替的正电荷和负电荷沿着的肽，因此具有以电荷序列依赖性方式自组装成聚集体的能力。 最近我们研究了模型肽的自组装（即，EAK 16）主要在单链水平上使用蒙特卡罗（MC）模拟。 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，链内塌陷和链间碰撞的时间），并研究它们对肽自组装的影响。

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.