Understanding Non-covalent Interactions in Carbon-Nanotube Bioconjugates

描述(申请人提供)：碳纳米管(CNT)由生物分子功能化，因其在生物医学方面的应用前景而备受关注，例如，用于治疗目的的新型药物、DNA和蛋白质转运体。非共价相互作用广泛存在于碳纳米管-生物结合物中，对碳纳米管在水溶液中的溶解性和碳纳米管在活细胞中的内化起着非常重要的作用。然而，碳纳米管-生物系统中如此弱的相互作用远未在分子水平上得到很好的理解。该项目的主要目标是利用最先进的基于第一性原理的工具，如密度泛函理论计算、量子和经典分子动力学模拟，很好地理解碳纳米管-生物结合物之间的非共价相互作用。该项目的目标是： (1)验证合适的密度泛函理论和基于第一原理的描述碳纳米管与DNA碱基、氨基酸、多肽等生物分子之间的非共价相互作用和电荷转移的有效方法； (2)在分子水平上为碳纳米管与DNA碱基、氨基酸、DNA寡核苷酸和多肽等生物分子之间的非共价相互作用的性质提供基准结果； (3)通过多尺度分子模拟和模拟，阐明碳纳米管与DNA-蛋白质体系之间非共价相互作用的几个重要问题，如相互作用机理、主要驱动力、相互作用与单壁碳纳米管直径和电子结构的关系、相互作用与多肽和DNA寡核苷酸组成和序列的关系； (4)了解SWCNT-生物分子偶联物进入活细胞的细胞内化机制。 开发新型高效的给药系统对提高药物分子的治疗水平具有重要意义。碳纳米管功能化的进展为这一领域开辟了新的可能性。通过对生物分子与碳纳米管界面和相互作用的理论研究，可以从分子水平上理解和描述碳纳米管-生物偶联物。这些知识最终可能有助于设计基于碳纳米管的新一代药物输送系统。

DESCRIPTION (provided by applicant): Carbon nanotubes (CNT), functionalized by biomolecules, are attracting much attention because of their promising biomedical applications, for instance, using as novel drug, DNA and protein transporters for therapy purposes. Non-covalent interactions widely exist in CNT-bioconjugates and play very important roles on solubility in aqueous solutions and internalization of CNT into living cells. However, such weak interactions in CNT-biosystems are far from being well understood at a molecular level. The major goal of the project is to well understand the non-covalent interactions among the CNT-bioconjugates with state-of-the-art first principles based tools such as density functional theory calculation, quantum and classical molecular dynamics simulations. The objectives of the project are: (1) to validate an appropriate density functional theory as well as an effective first principle-based protocol to describe non-covalent interactions and charge transfer between CNTs and biomolecules such as DNA bases, amino acids, polypeptides and so on; (2) to provide benchmark results at a molecular level for the nature of the non-covalent interactions between CNTs and biomolecules like DNA bases, amino acids, DNA oligonucleotides, and polypeptides; (3) to clarify a few important issues for the non-covalent interactions between CNT and DNA-protein systems via multi-scale molecular modeling and simulations, such as interaction mechanism, the major driving force, interaction dependence on the diameters and electronic structure of single-walled CNTs (SWCNTs), and interaction dependence on the composition and sequence of polypeptide and DNA oligonucleotides; (4) to well understand cellular internalization mechanisms of SWCNT-biomolecule conjugates into living cells. Development of new and efficient drug delivery system is very important to improve the therapeutic profile of drug molecules. The advancement of carbon nanotube functionalization has opened up new possibilities in this field. Theoretical investigations of the interface and interactions between biomolecules and CNT could provide understanding and description for CNT-bioconjugates at a molecular level. Such knowledge could eventually help design a new generation of drug delivery systems based on CNTs.