Simulation of Self-Assembly

The assembly of nanoscale materials and devices with useful structural, mechanical and electrical properties presents a great challenge for the future. A very promising approach is offered by self-assembly processes, in which nanoscopic or colloidal building blocks combine spontaneously to form ordered structures. While top-down approaches to assembly become increasingly challenging on small length scales, self-assembly offers a bottom-up approach which circumvents many of these difficulties.Biological systems display an astonishing variety of ordered and precise self-assembly processes. For example, the process of virus replication involves the assembly of hundreds of proteins to form highly symmetric shells called capsids. Such systems provide inspiring examples of the level of control possible in self-assembly. Future applications in nanotechnology are likely to require this level of sophisticated control in order to form precisely ordered structures, with specific chemical and physical properties of technological importance.To achieve such targets will require not only experimental advances in the synthesis of the building blocks for self-assembly, but also a deep theoretical understanding of the fundamental principles of self-assembly and the design rules for creating new self-assembling materials with useful structural, electronic, or optoelectronic properties. Computer simulation provides the tools for discovering these design principles, for example through direct visualization of the microscopic mechanisms of self-assembly. However, in many cases there is a large gap in length and time scales between the systems it is feasible to study computationally, and those of interest to experimentalists. The principal aim of the current project is to develop a variety of new computational tools that are required to overcome these obstacles to simulating self-assembly, and to apply them to understand the structures, thermodynamics and dynamics of both biological and synthetic self-assembling systems. To this end, we have assembled an experienced team with complementary research skills in the fields of structure analysis and optimisation, development of potential and free energy models, dynamics, thermodynamics, landscape analysis and visualisation.Our project involves several interdependent themes. One key aim is to understand and control size selection for self-assembling shells, helices and other interesting morphologies, including knotted topologies. Here we will employ direct simulation, and seek to explain the observed behaviour using a new method for visualising the complex landscape corresponding to favourable structures, kinetic traps, and the pathways that link them. We will combine two existing methods for studying rare events to exploit the best features of each one in a hybrid approach, where geometry optimisation is used to identify the pathways, and reaction rates are evaluated accurately using detailed dynamics. We also aim to simulate nucleation and crystallisation of bulk phases with interesting structures, which might exhibit novel properties of technological importance. Here we would predict the organisation of bulk phases along with the corresponding phase diagrams. A key objective of this project is to predict suitable building blocks for self-assembly of structures with specific properties at a coarse-grained level. By discovering the critical interparticle forces that determine the outcome of the self-assembly process we will guide new experiments. Here we need to define parameters such as the shape of the particles and the way they bind together. We will also investigate hierarchical self-assembly, where structures that form in the first step are used as the building blocks for subsequent steps in the creation of even larger and potentially more complex materials. This investigation will suggest experimental routes to multi-component nanoscale structures.

This project addresses a key area identified by the 2009 International Review of UK Chemistry as 'in need of emphasis and encouragement', recommending `Integration of computational chemistry (Need to enhance the participation of theory and computation especially in areas that involve energy, materials and health applications)'. In the area of human health, for example, a deeper understanding of self-assembly pathways will provide guiding principles for interfering with, disrupting, and potentially controlling such paths in amyloid formation associated with neurodegenerative diseases, and in the context of viral replication. The materials science aspects of the project will also have impact on society, as they may lead to the design of improved liquid crystal systems for device applications. Our research has the potential to expand the use of computer simulation in industrial applications concerned with developing new drugs and materials. We have active collaborations with leading experimental groups in self-assembly, and direct contacts with industry. Understanding the design principles for creating new self-assembling materials with specific properties will directly benefit UK industry. Advances in methodology will also find applications in pharmaceutical research, including ongoing partnerships with Evotec OAI and Eli Lilly. The programme is also directly relevant to a new consortium involving Syngenta and Unilever. We plan to interact directly with experimentalists and industrial scientists who are interested in simulating and designing self-assembling systems. The exploitation and protection of any results with commercial potential deriving from the project will be handled through the Research Services Divisions of the Universities of Cambridge, Oxford and Birmingham, which have considerable experience in this area. A project currently under development with Eli Lilly would facilitate direct knowledge transfer to industry. The Programme will provide excellent professional training for the PDRAs and PhD students to be appointed, allowing them to gain additional, valuable research-specific and generic skills. All participants will benefit significantly from working in strong research groups with strong links to experimental groups and to industry. The regular meetings to be held between the participants, and exchanges between the research groups will also benefit the PDRAs and PhDs. They will also gain valuable experience of writing up their research for publication and presenting it at national and international conferences. Results will be published in high profile, peer-reviewed journals. [The applicants have an excellent track record in publishing in such journals, with 12 papers in Nature, 8 in Science and 63 in Physical Review Letters to date.] Appropriate funding is requested to attend important national and international conferences to disseminate results. During the course of the Programme, several articles will also be written for publication in general science journals and we undertake to increase the public understanding of science through giving public lectures. We will provide online web-based access to data that may be useful to other researchers. For example, new structural data will be deposited in the Cambridge Cluster Database (http://www-wales.ch.cam.ac.uk/CCD.html), which is a web resource that is now exploited by many research groups around the world. All the computer codes that we develop will be made available for use under the Gnu public software licence (GPL). The applicants are all experienced in disseminating such programs and providing documentation and support. Separate web sites will be developed for the current project, both for our own internal data exchange, and to provide specific documentation and example input and output for self-assembly simulations.