45792-G6
Understanding Molecular Transport in Carbon Nanotubes
This project studies the interaction between carbon nanotubes and other molecules, including peptidomimetics, by means of molecular modeling and simulations. Carbon nanotubes are aromatic systems with high polarizabilities; however, most studies based on molecular mechanics models have ignored the role of electrostatics in the interaction. To address this challenge, we have developed a polarizable atomic multipole electrostatic model for the carbon nanotubes. This model is capable of describing the electrostatic interactions and polarization response via polarizable point multipoles. Using an atomic polarizability of 1.75 A^3 for C, 0.696 for H, we are able to reproduce the molecular polarizability tensor of benzene, naphthalene, anthracene, and a carbon nanotube reasonably well in comparison with experimental and DFT results. The parameters have been included in TINKER distribution, and can be used with proteins and a range of small molecules.
We also investigated the conformational properties of synthetic polydepsipeptides using molecular dynamics simulations. Depsipeptide is a chemical structure consisting of both ester and amide bonds. We calculated the quantum mechanics to compute depsidipeptide conformational energy in gas and solution phases. Similar to an alanine dipeptide, the depsidipeptide exhibits a strong preference for polyproline II (PPII) conformation. In addition, because of the changes in the intramolecular interaction due to the presence of ester group, the propensity for beta-sheets and alpha-helices decreased while a high population at (f, ψ) = (-150°, 0°) conformation was observed. With a molecular mechanics model developed based on the quantum mechanical study, both simulated annealing and replica exchange molecular dynamics simulations have been performed on oligodepsipeptides with alternating depsi and natural residues in solution. Novel helical structures have been determined from the simulations. When glycine is used as the alternating natural amino acid residue, the PPII conformation of depsi residue stabilizes the peptide into a right-handed helical structure while the alpha-helical conformation of depsi residue leads to an overall left-handed helical structure. The free energy analysis indicates that both the left- and right-handed helices are equally likely to exist. When charged, lysine is introduced as the alternating natural residue; however, the depsipeptide sequence prefers an extended conformation as in PPII predominantly. Our results indicate that the depsipeptide is potentially useful in designing protein mimetics with controllable structure and chemistry.
Overall, our research results have demonstrated that a simple classical model is effective in modeling the electrostatic response of nanotubes to external field. Novel foldamers based depsipeptide have been suggested from molecular simulations. The remaining funding will allow us to study the interaction of carbon-based nanostructures and other molecular systems including synthetic peptidomimetics for potential applications in materials and biomedical science.
The PRF starter grant greatly facilitated the establishment of my research program at the beginning of my academic career. With the financial support provided by ACS PRF, the graduate and undergraduate students were able to focus on the research and made noteworthy progress, including publishing one peer-reviewed journal article.
