Moore's Law states that the number of active components on an microchip doubles every 18 months. Variants of this Law can be applied to many measures of computer performance, such as memory and hard disk capacity, and to reductions in the cost of computations. Remarkably, Moore's Law has applied for over 50 years during which time computer speeds have increased by a factor of more than 1 billion! This remarkable rise of computational power has affected all of our lives in profound ways, through the widespread usage of computers, the internet and portable electronic devices, such as smartphones and tablets. Unfortunately, Moore's Law is not a fundamental law of nature, and sustaining this extraordinary rate of progress requires continuous hard work and investment in new technologies most of which relate to advances in our understanding and ability to control the properties of materials. Computer software plays an important role in enhancing computational performance and in many cases it has been found that for every factor of 10 increase in computational performance achieved by faster hardware, improved software has further increased computational performance by a factor of 100. Furthermore, improved software is also essential for extending the range of physical properties and processes which can be studied computationally. Our EPSRC Centre for Doctoral Training in Computational Methods for Materials Science aims to provide training in numerical methods and modern software development techniques so that the students in the CDT are capable of developing innovative new software which can be used, for instance, to help design new materials and understand the complex processes that occur in materials. The UK, and in particular Cambridge, has been a pioneer in both software and hardware since the earliest programmable computers, and through this strategic investment we aim to ensure that this lead is sustained well into the future.

Wherever advanced materials are required for technology theory and simulation have a vital role to play. That role may be in making a safety case, or reducing costs by narrowing down the selection of materials, or predicting and preventing failures. It may also be to establish whether and how materials may be designed to meet engineering specifications, or to interpret experimental characterizations of materials over a range of length and time scales.The need for this DTC cannot be overstated: there are no longer PhD graduates produced anywhere in the UK with a foundation knowledge of theoretical and computational materials physics. Current PhD graduates in theory and simulation of materials (TSM), with a first degree in a subject other than materials science, know extremely little about materials physics beyond the topic of their own research. On the other hand very few students with a first degree in materials science have sufficient training in mathematical techniques to engage in TSM at any level beyond the use of standard simulation packages. The need for breadth in the training of PhD graduates in TSM stems directly from the multi-scale and multi-physics nature of the vast majority of challenging problems in materials technology. The need exists both in industrial and academic research. The education and training provided by the DTC will be unique in the UK. For the first time in decades students will be taught theoretical materials physics at a sophisticated mathematical level, which will enable them to model the principal classes of materials across the length and time scales. They will also learn about the principal techniques of simulating materials at different length and time scales, and how information is transferred up and down the length and time scale hierarchies. The multidisciplinary training and research environment of the DTC, in combination with a wide range of cohort building and student empowerment activities, will provide a far richer educational and professional experience than a standard PhD funded through the DTA. The scientific network students will be able to form through the DTC with their peers, academics, industrialists and leading visiting scientists will be a lasting benefit for them.The DTC will bring together key staff of 4 departments across 2 faculties at Imperial College. Students will have 2 supervisors, whose expertise will not be centred at the same length scale. This will usually mean that their supervisors are in different departments. Similarly, no single department has the expertise to provide the range of courses that students will receive in their first year. For these reasons the multidisciplinary training and research environment can be delivered only through a DTC. Conversely, if the DTC is not funded then narrowly focused PhDs in TSM will continue to be generated with the same limited usefulness for industry, academe and the students themselves as they have in the past 2-3 decades.With nuclear power once again a key component of the Government strategy for energy there will be a significant demand from this sector for graduates of the DTC, as confirmed by the letter of support from UKAEA. Other forms of producing energy such as wind and solar power will also benefit. But TSM is needed in all advanced materials technologies, including aerospace and land-based transportation, building and construction, the processing, storage and communication of information, sport, prostheses and health-care, sensors and security, defence and more. The need from academic groups in the UK and overseas is also very significant. Indeed the absence of suitably trained PhD graduates is universally recognised in the attached letters of support from academics, national labs and industry, as one of their principal concerns. Judging by these letters the 50 graduates of the DTC funded by EPSRC are likely to be in very strong demand.

The Industrial Doctorate Centre in Molecular Modelling and Materials Science (M3S) at University College London (UCL) trains researchers in materials science and simulation of industrially important applications. As structural and physico-chemical processes at the molecular level largely determine the macroscopic properties of any material, quantitative research into this nano-scale behaviour is crucially important to the design and engineering of complex functional materials. The M3S IDC is a highly multi-disciplinary 4-year EngD programme, which works in partnership with a large base of industrial sponsors on a variety of projects ranging from catalysis to thin film technology, electronics, software engineering and bio-physics research. The four main research themes within the Centre are 1) Energy Materials and Catalysis; 2) Information Technology and Software Engineering; 3) Nano-engineering for Smart Materials; and 4) Pharmaceuticals and Bio-medical Engineering. These areas of research align perfectly with EPSRC's mission programmes: Energy, the Digital Economy, and Nanoscience through Engineering to Application. In addition, per definition an industrial doctorate centre is important to EPSRC's priority areas of Securing the Future Supply of People and Towards Better Exploitation. Students at the M3S IDC follow a tailor-made taught programme of specialist technical courses, as well as professionally accredited project management courses and transferable skills training, which ensures that whatever their first degree, on completion all students will have obtained thorough technical and managerial schooling as well as a doctoral research degree. The EngD research is industry-led and of comparable high quality and innovation as the more established PhD research degree. However, as the EngD students spend approximately 70% of their time on site with the industrial sponsor, they also gain first hand experience of the demanding research environment of a successful, competitive industry. Industrial partners who have taken up the opportunity during the first phase of the EngD programme to add an EngD researcher to their R&D teams include Johnson Matthey, Pilkington Glass, Exxon Mobil, Silicon Graphics, Accelrys and STS, while new companies are added to the pool of sponsors each year. Materials research in UCL is particularly well developed, with a thriving Centre for Materials Research and a newly established Materials Chemistry Centre. In addition, the Bloomsbury campus has perhaps the largest concentration of computational materials scientists in the UK, if not the world. Although affiliated to different UCL departments, all computational materials researchers are members of the UCL Materials Simulation Laboratory, which is active in advancing the development of common computational methodologies and encouraging collaborative research between the members. As such, UCL has a large team of well over a hundred research-active academic staff available to supervise research projects, ensuring that all industrial partners will be able to team up with an academic in a relevant research field to form the supervisory team to work with the EngD student. The success of the existing M3S Industrial Doctorate Centre and the obvious potential to widen its research remit and industrial partnerships into new, topical materials science areas, which are at the heart of EPSRC's strategic funding priorities for the near future, has led to this proposal for the funding of 5 annual cohorts of ten EngD students in the new phase of the Centre from 2009.

The Centre for Doctoral Training in "Molecular Modelling and Materials Science" (M3S CDT) at University College London (UCL) will deliver to its students a comprehensive and integrated training programme in computational and experimental materials science to produce skilled researchers with experience and appreciation of industrially important applications. As structural and physico-chemical processes at the molecular level largely determine the macroscopic properties of any material, quantitative research into this nano-scale behaviour is crucially important to the design and engineering of complex functional materials. The M3S CDT offers a highly multi-disciplinary 4-year doctoral programme, which works in partnership with a large base of industrial and external sponsors on a variety of projects. The four main research themes within the Centre are 1) Energy Materials; 2) Catalysis; 3) Healthcare Materials; and 4) 'Smart' Nano-Materials, which will be underpinned by an extensive training and research programme in (i) Software Development together with the Hartree Centre, Daresbury, and (ii) Materials Characterisation techniques, employing Central Facilities in partnership with ISIS and Diamond. Students at the M3S CDT follow a tailor-made taught programme of specialist technical courses, professionally accredited project management courses and generic skills training, which ensures that whatever their first degree, on completion all students will have obtained thorough technical schooling, training in innovation and entrepreneurship and managerial and transferable skills, as well as a challenging doctoral research degree. Spending >50% of their time on site with external sponsors, the students gain first-hand experience of the demanding research environment of a competitive industry or (inter)national lab. The global and national importance of an integrated computational and experimental approach to the Materials Sciences, as promoted by our Centre, has been highlighted in a number of policy documents, including the US Materials Genome Initiative and European Science Foundation's Materials Science and Engineering Expert Committee position paper on Computational Techniques, Methods and Materials Design. Materials Science research in the UK plays a key role within all of the 8 Future Technologies, identified by Science Minister David Willetts to help the UK acquire long-term sustainable economic growth. Materials research in UCL is particularly well developed, with a thriving Centre for Materials Research, a Materials Chemistry Centre and a new Centre for Materials Discovery (2013) with a remit to build close research links with the Catalysis Technology Hub at the Harwell Research Complex and the prestigious Francis Crick Institute for biomedical research (opening in 2015). The M3S will work closely with these centres and its academic and industrial supervisors are already heavily involved with and/or located at the Harwell Research Complex, whereas a number of recent joint appointments with the Francis Crick Institute will boost the M3S's already strong link with biomedicine. Moreover, UCL has perhaps the largest concentration of computational materials scientists in the UK, if not the world, who interact through the London-wide Thomas Young Centre for the Theory and Simulation of Materials. As such, UCL has a large team of well over 100 research-active academic staff available to supervise research projects, ensuring that all external partners can team up with an academic in a relevant research field to form a supervisory team to work with the Centre students. The success of the existing M3S CDT and the obvious potential to widen its research remit and industrial partnerships into topical new materials science areas, which lie at the heart of EPSRC's strategic funding priorities and address national skills gaps, has led to this proposal for the funding of 5 annual student cohorts in the new phase of the Centre.

The search for new medicinal entities within the pharmaceutical industry is a critical problem. Early stage lead identification and optimization often exploits knowledge of the interaction between a putative drug, and a target enzyme or other macromolecular system. Consequently in recent years there has been exponential growth in the number of protein structures (e.g. 53 thousand structures in the RCSB Protein Data Bank) and similar growth has been observed with proprietary structure data in the pharmaceutical industry. In parallel to the growth of available structure data, significant research effort has been directed towards understanding the possible interactions of small molecules and the protein structures. Most commonly this has been through empirical docking schemes whose main focus has been to provide fast identification of an approximate binding pose. Speed is important because of the enormous size of the compound collections that need to be virtually 'screened'. These schemes provide a very reasonable estimation of the binding pose; however they almost universally fail when used to estimate differences in binding affinity. This failure is due to the approximations made in their construction. Specifically, even when physical interactions between protein and ligands are considered in an atomistic way, they are described by classical potentials, so molecules are represented as balls (atoms) connected with springs (bonds). In general this precludes the inclusion of any form of polarization of ligand or protein, or electronic charge transfer between the moieties. To get an accurate representation of such interactions one needs to use a full Quantum Mechanical (QM) representation of the system. Application of QM methods from 'first principles' to systems as large as protein-ligand complexes has until recently been beyond the scope of any available methods, due to prohibitive computational cost which scales asymptotically as ~N^3 or worse, where N is the number of atoms. Even on supercomputers, these methods are limited to no more than a few hundred atoms while most proteins of interest contain thousands of atoms. Recently the ONETEP first principles method has been developed where the computational cost scales only as ~N (linear-scaling) and is capable of calculations with thousands of atoms. The ONETEP method was originally developed and validated in the context of Materials Science simulations. The main focus of the proposed research would be application of ONETEP to a number of biological systems. The work will answer several questions such as: the ability of the method to correctly predict the relative binding affinity of series of potential drugs and the analysis of binding mechanism through visual and numerical processing of the electronic structure (density, molecular orbitals) of the complex in a full QM framework. Reliable modelling of mechanisms such as charge transfer are key to correct understanding of interactions for example in the heme group in CYP p450 enzymes - which play a central role in human metabolism. Calculations on the CYP p450s, and any other metal-containing systems, cannot be accurately performed without some consideration of the full QM effects. Previous efforts included QM/MM approaches, where a small portion of the biomolecule is treated in a QM fashion and the rest is described with classical potentials. A major concern of these approaches is the quality of the coupling between the classical and quantum regions as well as the size of the quantum region (usually too small, for computational reasons). ONETEP will therefore also provide absolute benchmarks for QM/MM approaches by treating quantum mechanically the entire biomolecule. The current proposal would provide vital validation of the linear-scaling first principles QM methodology in biomolecular simulations, which is critical before any widespread adoption of the methods within the pharmaceutical industry.