Understanding Non-covalent Interactions in Carbon-Nanotube Bioconjugates

描述（由申请人提供）：通过生物分子功能化的碳纳米管（CNT）由于其有前途的生物医学应用而吸引了很多关注，例如，用作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-生物复合物中，对碳纳米管在水溶液中的溶解性和在活细胞中的内化起着非常重要的作用。然而，CNT-生物系统中的这种弱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CNT-生物缀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以及有效的基于第一性原理的方案来描述碳纳米管与生物分子如DNA碱基、氨基酸、多肽等之间的非共价相互作用和电荷转移; (2)在分子水平上提供CNT与生物分子（如DNA碱基、氨基酸、DNA寡核苷酸和多肽）之间非共价相互作用性质的基准结果; (3)通过多尺度分子模拟，阐明了碳纳米管与DNA-蛋白质体系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、相互作用对单壁碳纳米管（SWCNTs）直径和电子结构的依赖性、相互作用对多肽和DNA寡核苷酸组成和序列的依赖性; (4)更好地理解SWCNT-生物分子缀合物进入活细胞的细胞内化机制。 开发新型高效的药物传递系统对提高药物分子的治疗效果具有重要意义。碳纳米管功能化的进展为该领域开辟了新的可能性。生物分子与碳纳米管之间的界面和相互作用的理论研究可以提供在分子水平上理解和描述碳纳米管-生物缀合物。这些知识最终可能有助于设计基于CNT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.