Theoretical studies in charged biomolecules

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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.