NER: Simulation Strategies for Biomolecular Assembly of Nanoscale Building Blocks

NER：纳米级构件的生物分子组装模拟策略

• 批准号: 0210551
• 负责人: Sharon Glotzer
• 金额: $ 10万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0210551&HistoricalAwards=false
• 关键词: NER; Simulation; Strategies; Biomolecular; Assembly

The Principal Investigator will develop a simulation strategy that can be used to elucidate the fundamental principles by which functionalized nanoscale building blocks (NBBs) are assembled into ordered structures using biomolecules as "linkers" or "connectors" between the NBBs. Recent pioneering experimental work has demonstrated that suitably functionalized NBBs can be assembled into rather simple ordered structures with specific properties and functionalities using biological or synthetic macromolecules as linkers. For example, nanoscopic gold particles ranging in size from 2 nm to 30 nm and functionalized by DNA, biotin, or synthetic polymers have been shown to assemble into three-dimensional hexatic close-packed structures and spheres extending over hundreds to thousands of nanometers. DNA, in essence a "digitally programmable" biomolecule, is especially intriguing as an "assembler" of NBBs because specific linker-linker interactions can be programmed by inserting purposely tailored complementary nucleotide sequences into different DNA strands.Aside from these exciting "proof-of-concept" studies, however, no systematic knowledge with regard to possible synthesis and processing strategies, nor the range of structures possible, for NBB/macromolecule assemblies has been obtained - not even the principal axes of the vast parameter space of these complex systems have been identified. Computer simulations will be instrumental in the effort to define and efficiently map out parameter space and provide fundamental insight to the assembly process. Despite advances in computational power and simulation algorithms, however, the disparate time and length scales that govern the staged, hierarchical ordering processes of NBBs and macromolecules in solution prohibit the immediate application of any one "off-the-shelf" simulation technique.In this project, the PI will explore several ideas for combining different well-known molecular and/or particle-based simulation methodologies with the specific aim of overcoming the disparate time scales on which the NBBs and macromolecule linkers move. She will consider the individual and combined use of several classical molecular or so-called "particle-based" simulation methods, including molecular dynamics, Brownian dynamics, and off-lattice Monte Carlo, in order to develop an overall simulation strategy capable of simulating NBB/biomolecule assemblies with as much chemical fidelity as possible given computational limitations. The focus will be on using DNA as assemblers, but the strategy will generally apply to other macromolecular linkers as well. NBB geometries that the simulation approach will be capable of modeling include spheres and polyhedra (e.g. gold nanoparticles, colloidal silica, Buckyballs, nanoprisms, CdSe quantum dots), nanorods, nanosheets (e.g. clays) and nanoaggregates (e.g. linear chain aggregates).The PI expects the proposed research to provide an important and necessary advance in the ability to model programmed macromolecular assembly of NBBs in general and DNA/NBB assemblies in particular. At the end of this one-year project, she will have tested several strategies for simulating DNA-assembled nanoparticle structures, and designed a comprehensive simulation methodology capable of modeling assemblies of NBBs of arbitrary composition and geometry joined by biomolecules or macromolecules of arbitrary chemical structure with classical simulation techniques. This methodology will provide researchers in the field of computational nanoscience with simulation strategies to support detailed investigations in nanoscale systems. Without these strategies, simulation science will likely be unable to contribute significantly to the quest for fundamental understanding and design principles for the self- and guided-assembly of nanoscale building blocks.

首席研究者将制定一种模拟策略，该策略可用于阐明基本原理，通过该原理将功能化的纳米级构建块（NBB）组装成使用生物分子作为“接头”或“连接器” NBBS之间的有序结构。最近的开创性实验工作表明，使用生物或合成大分子作为接头，可以将适当的功能化NBB组装成具有特定特性和功能的相当简单的有序结构。例如，已证明纳米尺寸从2 nm到30 nm，由DNA，生物素或合成聚合物功能化，可将其组装成三维六维的近距离封闭结构，并延伸到数百万至数千纳米纳米的范围内。 DNA本质上是一种“数字可编程”的生物分子，特别吸引了NBB的“组装程序”，因为可以通过将特定的链接器链接器进行编程，通过将目的定制的互补核苷酸序列插入不同的dna strand中，从而使这些令人兴奋的“策略”的范围和处理，并且可以从可能的范围内进行策略，并与这些策略相关的范围，以及可能的范围，以及对这些策略的进行范围，以及可能的范围。已经获得了NBB/大分子组件 - 甚至还没有鉴定出这些复杂系统的庞大参数空间的主要轴。计算机模拟将有助于定义和有效地绘制参数空间并为组装过程提供基本见解。尽管计算能力和仿真算法取得了进步，但是，控制NBB和大分子在解决方案中的分阶段，等级的分层订购过程的分散时间和长度尺度，禁止任何一个“现成”模拟技术的任何一个“仿真”技术与其他层次的构图相结合。 NBB和大分子接头移动的不同时间尺度。她将考虑几种经典分子或所谓的“基于粒子”的模拟方法的单独和联合使用，包括分子动力学，布朗动力学和局部蒙特卡洛，以制定能够模拟NBB/BioMolecules组件的整体模拟策略，并具有尽可能多的化学限制。重点将放在使用DNA作为组件上，但是该策略通常也适用于其他大分子接头。 NBB geometries that the simulation approach will be capable of modeling include spheres and polyhedra (e.g. gold nanoparticles, colloidal silica, Buckyballs, nanoprisms, CdSe quantum dots), nanorods, nanosheets (e.g. clays) and nanoaggregates (e.g. linear chain aggregates).The PI expects the proposed research to provide an important and necessary advance in通常，尤其是DNA/NBB组件对编程的大分子组装进行建模的能力。在这个为期一年的项目结束时，她将测试几种模拟DNA组装的纳米颗粒结构的策略，并设计了一种综合的模拟方法，能够对NBB的组成和几何形状与生物分子或具有分类化学仿真技术的任意化学结构的大分子的NBB组件进行建模。这种方法将为计算纳米科学领域的研究人员提供模拟策略，以支持纳米级系统中的详细研究。没有这些策略，模拟科学可能将无法为纳米级构建基块的自我和指导组装的基本理解和设计原则做出重大贡献。