NER: Simulation Strategies for Biomolecular Assembly of Nanoscale Building Blocks

主要研究者将开发一种模拟策略，该策略可用于阐明功能化纳米级构建块（NBBs）使用生物分子作为NBBs之间的“接头”或“连接器”组装成有序结构的基本原理。最近的开创性实验工作已经证明，适当官能化的NBBs可以组装成相当简单的有序结构，具有特定的性质和功能，使用生物或合成的大分子作为接头。例如，纳米级金颗粒的尺寸范围从2 nm到30 nm，并通过DNA，生物素或合成聚合物功能化，已被证明组装成三维六角密堆积结构和球体，延伸数百至数千纳米。DNA本质上是一种“数字可编程”的生物分子，作为NBBs的“组装器”特别有趣，因为可以通过将特意定制的互补核苷酸序列插入不同的DNA链来编程特定的接头-接头相互作用。然而，除了这些令人兴奋的“概念验证”研究之外，没有关于可能的合成和加工策略的系统知识，也没有可能的结构范围，对于NBB/大分子组装体，甚至还没有确定这些复杂系统的巨大参数空间的主轴。计算机模拟将有助于定义和有效地绘制出参数空间，并提供基本的洞察装配过程。尽管在计算能力和模拟算法的进步，然而，不同的时间和长度尺度，支配的阶段，分层排序过程的NBBs和大分子在解决方案禁止任何一个“现成的”模拟技术的直接应用。PI将探索几种用于组合不同公知分子和/或粒子的想法-基于模拟方法，其具体目的是克服NBBs和大分子连接体移动的不同时间尺度。她将考虑几个经典的分子或所谓的“基于粒子”的模拟方法，包括分子动力学，布朗动力学和非格子蒙特卡罗的单独和组合使用，以开发一个整体的模拟策略，能够模拟NBB/生物分子组件尽可能多的化学保真度给定的计算限制。重点将是使用DNA作为组装器，但该策略通常也适用于其他大分子连接体。仿真方法能够建模的NBB几何形状包括球体和多面体（例如，金纳米颗粒、胶态二氧化硅、巴基球、纳米棱镜、CdSe量子点），纳米棒，纳米片（例如粘土）和纳米聚集体PI预计，拟议的研究将在对NBBs的程序化大分子组装进行建模的能力方面提供重要和必要的进展，并且DNA/DNA聚合物的程序化大分子组装将在未来几年内完成。特别是NBB组件。在这个为期一年的项目结束时，她将测试几种模拟DNA组装纳米颗粒结构的策略，并设计一种全面的模拟方法，能够模拟任意组成和几何形状的NBBs组件，这些组件由生物分子或具有任意化学结构的大分子组成。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，以支持纳米级系统的详细调查。如果没有这些策略，模拟科学可能无法为寻求纳米级构建块的自组装和引导组装的基本理解和设计原则做出重大贡献。

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.