Proteins/Peptides Transportation In Carbon Nanotubes: A MD Study

Carbon nanotubes (CNTs), featuring unique structure and amazing properties, have been considered in numerous studies owing to their diverse potential applications. Recently, many studies suggest that CNTs could serve as nanoscale pipes to deliver fluids and molecular species. Thanks to the deep potential well inside the CNT interior, it is generally easy to encapsulate molecules, which makes it a unique system for studying nanofluidics and molecular transport. In particular, its ability to serve as biocompatible transporters in medicine and drug delivery has received more and more attention. In addition, both covalent and noncovalent functionalizations have opened up opportunities for medical diagnostic purposes and drug delivery applications. So far, many biomolecules and drugs have been found to be encapsulated into the inner space of CNTs spontaneously from both computational and experimental studies, in case that these guest molecules have suitable size. In spite of these exciting observations on various molecules encapsulated into CNTs, the dynamic mechanisms of these encapsulation processes at the molecular level remain bscure, which limits the biological and biomedical applications of CNTs. To this end, the molecular simulation helps ones to better understand the dynamic mechanism in the bio-nano-systems, and establish new concepts for controlling/tuning the performance of such systems to facilitate the design and optimization of CNT-based functional nanoscale devices.In this thesis molecular dynamics (MD) simulation and steered MD simulation were performed to investigate spontaneous encapsulation of proteins/peptides in CNTs, as well as the the atomic details of the interactions taking place at the molecular level, and the dynamic mechanisms of the biomolecules-CNT systems.1. MD simulations demonstrate that a collagen-like peptide with a hydrophobic center and hydrophilic surfaces could be inserted into CNTs spontaneously but slowly. Then the dynamic mechanism of the encapsulation process was investigated by a series of steered molecular dynamics simulations. The van der Waals interaction between the peptide and the carbon nanotubes was proved to be a positive factor for this insertion process, whereas the major resistance of this process is attributed to the repelling of the trapped water molecules and the breaking of the hydrogen-bond networks of water molecules around the peptide.2. A spontaneous encapsulation of a globular protein in the CNT was observed through MD simulations. The free energy of the system was found to be decreased after the encapsulation, which is the most fundamental reason for this spontaneous process. The system enthalpy decrease was found to make a dominant contribution to the free-energy change, and the system entropy increase also contributes to the spontaneous process. During the insertion, the protein makes a stepwise conformational change to maximize its affinity to the CNT walls as well as the protein-CNT interactions, mainly resulting in the deformation of theβ-sheets in the protein. The CNT was considered to attract protein molecules nonspecifically although the groups with high hydrophobicity and/or aromatic rings show great affinity.3. The diameter selectivity of the protein/peptide encapsulation in CNTs was explored via MD simulations, and the free energy changes of the systems were calculated for mechanism exploration. An overlarge CNT provides insufficient van der Waals attraction to the protein/peptide, whereas too small a CNT hinders this spontaneous process due to the increasing resistance from the solvent. From the perspective of the free energy change of the whole system, the insufficient energy well of the system with the overlarge CNT makes the spontaneous process be hardly observed in the time scale of our simulations, whereas a remarkable energy barrier of the system with the overcrowded CNT resists the protein/peptide in the CNT entrance. In addition, the significance of the solvents for the system is also of concern.4. The influence of chirality on the peptide encapsulation in CNTs was investigated using MD simulations. The simulations indicate that the encapsulation of an α-helix peptide depends on the chirality of CNTs. For CNTs with similar diameters and lengths, nanotubes with larger chiral angles achieve higher interaction energy. The diffusion energy barrier of water molecules in armchair CNTs is much lower than that in zigzag CNTs, which affects the dynamic behaviors of biomacromolecules in systems.