First-Principles, Computer-Aided Nanosystem Design and Analysis

描述(由申请人提供)：通过开发用于计算机辅助设计的软件来解决在设计用于医疗应用的纳米结构时遇到的困难。我们的软件将基于严格的多尺度分析，以捕捉原子和整个纳米系统的特征。通过在多尺度框架内使用原子间力场，将实现广泛的适用性。我们将解决的纳米颗粒问题包括(1)与选定的目标病变细胞的相互作用，(2)热力学稳定性，(3)循环系统内的畅通运输，(4)有效载荷治疗药物在病变组织的定时释放，(5)货架期，以及(6)防止聚集。这些因素将在温度、盐度和化学条件的特定范围内得到解决。为了实现这些目标，将创建一个纳米系统模拟器Nanox，以弥合原子和纳米结构的规模。传统的分子动力学程序不能在生物相关的时间尺度(即毫秒或更长)上模拟这些超百万原子系统。我们开发了一种新的算法，它基于有序参数的自动构建，它表征了整个纳米尺度的特征，以及一种多尺度方法，能够在允许大规模空间和时间尺度计算的同时保留基本的原子细节。我们将完成Nanox的全面实施，使用病毒衣壳数据对其进行测试，并通过使用脂质体数据作为验证来展示其作为计算机辅助设计工具的能力。我们将把Nanox作为在线、开源软件免费提供。 与公共健康相关：开发了用于设计和分析纳米颗粒和纳米胶囊的软件，这些应用包括医学成像和靶向递送治疗剂和基因。该软件将改进癌症和基因治疗的策略，改进医学成像，并开发磁场引导的癌症治疗方法，以定位肿瘤或组织损伤的部位。

DESCRIPTION (provided by applicant): The difficulties encountered in designing nanoconstructs for medical applications are addressed by developing software for computer-aided design. Our software will be based on a rigorous multiscale analysis to capture both atomic and overall nanosystem features. Broad applicability will be achieved through the use of an interatomic force field within the multiscale framework. Nanoparticle issues we will address include (1) the interaction with selected target diseased cells, (2) thermodynamic stability, (3) unimpeded transport within the circulatory system, (4) timed release of payload therapeutics at diseased tissue, (5) shelf life, and (6) prevention of aggregation. These factors will be addressed across specific ranges of temperature, salinity, and chemical conditions. To accomplish these objectives, a nanosystem simulator, NanoX, will be created to bridge the atomistic and nanostructure scales. A conventional molecular dynamics code cannot simulate these supramillion atom systems over biologically relevant timescales (i.e., milliseconds or longer). We have developed a novel algorithm based on the automated construction of order parameters, which characterizes overall nanoscale features, and a multiscale methodology that enables retention of essential atomistic detail while allowing large spatial and temporal scale computations. We will complete the full implementation of NanoX, test it using data on viral capsids, and demonstrate its capabilities as a computer-aided design tool by using data on liposomes as validation. We will make NanoX freely available as online, open-source software. PUBLIC HEALTH RELEVANCE: Software is developed for designing and analyzing nanoparticles and nanocapsules for applications that include medical imaging and the targeted delivery of therapeutic agents and genes. This software will lead to improved strategies for cancer and gene therapy, refined medical imaging, and the development of magnetic field-guided cancer treatments to the site of the tumor or tissue damage.