Peter Coveney

University College London | UCL · Department of Chemistry

Substantial effort is being invested in the creation of a virtual human—a model which will improve our understanding of human physiology and diseases and assist clinicians in the design of personalised medical treatments. A central challenge of achieving blood flow simulations at full-human scale is the development of an efficient and accurate appr...

In recent years, it has become increasingly common for high performance computers (HPC) to possess some level of heterogeneous architecture - typically in the form of GPU accelerators. In some machines these are isolated within a dedicated partition, whilst in others they are integral to all compute nodes - often with multiple GPUs per node - and p...

Substantial effort is being invested in the creation of a virtual human — a model which will improve our understanding of human physiology and diseases and assist clinicians in the design of personalised medical treatments. A central challenge of achieving blood flow simulations at full-human scale is the development of an efficient and accurate ap...

In recent years, it has become increasingly common for high performance computers (HPC) to possess some level of heterogeneous architecture - typically in the form of GPU accelerators. In some machines these are isolated within a dedicated partition, whilst in others they are integral to all compute nodes - often with multiple GPUs per node - and p...

Many numerical studies of blood flow impose a rigid wall assumption due to the simplicity of its implementation compared to a full coupling with a solid mechanics model. In this paper, we present a localised method for incorporating the effects of elastic walls into blood flow simulations using the lattice Boltzmann method implemented by the open-s...

An arteriovenous fistula, created by artificially connecting segments of a patient’s vasculature, is the preferred way to gain access to the bloodstream for kidney dialysis. The increasing power and availability of supercomputing infrastructure means that it is becoming more realistic to use simulations to help identify the best type and location o...

Many numerical studies of blood flow impose a rigid wall assumption due to the simplicity of its implementation compared to a full coupling to a solid mechanics model. In this paper, we present a localised method for incorporating the effects of elastic walls into blood flow simulations using the lattice Boltzmann method. We demonstrate that our ap...

We present the VECMA toolkit (VECMAtk), a flexible software environment for single and multiscale simulations that introduces directly applicable and reusable procedures for verification, validation (V&V), sensitivity analysis (SA) and uncertainty quantication (UQ). It enables users to verify key aspects of their applications, systematically compar...

Many scientific and medical researchers are working towards the creation of a virtual human—a personalized digital copy of an individual—that will assist in a patient’s diagnosis, treatment and recovery. The complex nature of living systems means that the development of this remains a major challenge. We describe progress in enabling the HemeLB lat...

An arteriovenous fistula, created by artificially connecting segments of a patient's vasculature, is the preferred way to gain access to the bloodstream for kidney dialysis. The increasing power and availability of supercomputing infrastructure means that it is becoming more realistic to use simulations to help identify the best type and location o...

In recent years, it has become possible to calculate binding affinities of compounds bound to proteins via rapid, accurate, precise and reproducible free energy calculations. This is imperative in drug discovery as well as personalized medicine. This approach is based on molecular dynamics (MD) simulations and draws on sequence and structural infor...

A central quantity of interest in molecular biology and medicine is the free energy of binding of a molecule to a target biomacromolecule. Until recently, the accurate prediction of binding affinity had been widely regarded as out of reach of theoretical methods owing to the lack of reproducibility of the available methods, not to mention their com...

In recent years, it has become possible to calculate binding affinities of compounds bound to proteins via rapid, accurate, precise and reproducible free energy calculations. This is imperative in drug discovery as well as personalized medicine. This approach is based on molecular dynamics (MD) simulations and draws on sequence and structural infor...

We apply the hit-to-lead ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and lead-optimization TIES (thermodynamic integration with enhanced sampling) methods to compute the binding free energies of a series of ligands at the A 1 and A 2A adenosine receptors, members of a subclass of the GPCR (G protein-coup...

Many scientific and medical researchers are working towards the creation of a virtual human - a personalised digital copy of an individual - that will assist in a patient's diagnosis, treatment and recovery. The complex nature of living systems means that the development of this remains a major challenge. We describe progress in enabling the HemeLB...

We present the VECMA toolkit (VECMAtk), a flexible software environment for single and multiscale simulations that introduces directly applicable and reusable procedures for verification, validation (V&V), sensitivity analysis (SA) and uncertainty quantification (UQ). It enables users to verify key aspects of their applications, systematically comp...

New applications that can exploit emerging exascale computing resources efficiently, while providing meaningful scientific results, are eagerly anticipated. Multi-scale models, especially multi-scale applications, will assuredly run at the exascale. We have established that a class of multi-scale applications implementing the heterogeneous multi-sc...

This short contribution introduces a theme issue dedicated to ‘Multiscale modelling, simulation and computing: from the desktop to the exascale’. It holds a collection of articles presenting cutting-edge research in generic multiscale modelling and multiscale computing, and applications thereof on high-performance computing systems. The special iss...

"For it is not the abundance of knowledge, but the interior feeling and taste of things, which is accustomed to satisfy the desire of the soul." (Saint Ignatius of Loyola). We argue that the boldest claims of big data (BD) are in need of revision and toning-down, in view of a few basic lessons learned from the science of complex systems. We point o...

Mechanical exfoliation techniques are widely used to create high quality graphene samples for analytical use. Increasingly, mechanical methods are used to create large quantities of graphene, yet there is surprisingly little molecular insight into the mechanisms involved. We study the exfoliation of graphene with sticky tape using molecular dynamic...

We describe our Multiscale Computing Patterns software for High Performance Multiscale Computing. Following a short review of Multiscale Computing Patterns, this paper introduces the Multiscale Computing Patterns Software, which consists of description, optimisation and execution components. First, the description component translates the task grap...

Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic ma...

T lymphocytes are stimulated when they recognise short peptides bound to class I proteins of the major histocompatibility complex (MHC) protein, as peptide-MHC complexes. Due to the diversity in T-cell receptor molecules together with both the peptides and MHC proteins they bind to, it has been difficult to design vaccines and treatments based on t...

The accurate identification of the specific points of interaction between G protein-coupled receptor (GPCR) oligomers is essential for the design of receptor ligands targeting oligomeric receptor targets. A coarse-grained molecular dynamics computer simulation approach would provide a compelling means of identifying these specific protein-protein i...

We introduce the lattice-Boltzmann code LB3D, version 7.1. Building on a parallel program and supporting tools which have enabled research utilising high performance computing resources for more than 16 years, LB3D version 7 provides a subset of the research code functionality as an open source project. Here, we describe the theoretical basis of th...

Optimisation of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly due to its lack of accuracy and reproducibility, as well as the long turnaround...

Binding free energies of bromodomain inhibitors are calculated with recently formulated approaches, namely ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling). A set of compounds is provided by GlaxoSmithKline, which represents a range of chemical funct...

The accurate prediction of the binding affinities of ligands to proteins is a major goal in drug discovery and personalised medicine. The time taken to make such predictions is of similar importance to their accuracy, precision and reliability. In the last few years, an ensemble based molecular dynamics approach has been proposed that provides a ro...

It is commonly agreed that the most challenging problems in modern science and engineering involve the concurrent and nonlinear interaction of multiple phenomena, acting on a broad and disparate spectrum of scales in space and time. It is also understood that such phenomena lie at the interface

The current interest in big data, machine learning and data analytics has generated the widespread impression that such methods are capable of solving most problems without the need for conventional scientific methods of inquiry. Interest in these methods is intensifying, accelerated by the ease with which digitized data can be acquired in virtuall...

We expect that multiscale simulations will be one of the main high performance computing workloads in the exascale era. We propose multiscale computing patterns as a generic vehicle to realise load balanced, fault tolerant and energy aware high performance multiscale computing. Multiscale computing patterns should lead to a separation of concerns,...

The MPI intercommunication framework was used for coupling of two lattice-Boltzmann solvers with suspended particles, which model advection and diffusion respectively of these particles in a carrier fluid. Simulation domain was divided into two parts, one with advection and diffusion, and the other with diffusion only (no macroscopic flow). Particl...

The purpose of statistical mechanics is to provide a route to the calculation of macroscopic properties of matter from their constituent microscopic components. It is well known that the macrostates emerge as ensemble averages of microstates. However, this is more often stated than implemented in computer simulation studies. Here we consider founda...

We report the first electronic structure calculation performed on a quantum computer without exponentially costly precompilation. We use a programmable array of superconducting qubits to compute the energy surface of molecular hydrogen using two distinct quantum algorithms. First, we experimentally execute the unitary coupled cluster method using t...

Computer simulation is finding a role in an increasing number of scientific disciplines, concomitant with the rise in available computing power. Realizing this inevitably requires access to computational power beyond the desktop, making use of clusters, supercomputers, data repositories, networks and distributed aggregations of these resources. Acc...

We present FabSim, a toolkit developed to simplify a range of computational tasks for researchers in diverse disciplines. FabSim is flexible, adaptable, and allows users to perform a wide range of tasks with ease. It also provides a systematic way to automate the use of resourcess, including HPC and distributed resources, and to make tasks easier t...

We describe the mechanism that leads to full exfoliation and dispersion of organophilic clays when mixed with molten hydrophilic polymers. This process is of fundamental importance for the production of polymer-clay nanocomposites with enhanced materials properties. The chemically specific nature of our multiscale approach allows us to probe how ch...

Ab initio molecular dynamics simulations have been performed to gain an understanding of the interfacial microscopic structure and reactivity of fully hydrated clay edges. The models studied include both micropore and interlayer water. We identify acidic sites through dissociation mechanisms; the resulting ions can be stabilized by both micropore a...

In this paper we give a brief overview of the three projects that were chosen for XSEDE-PRACE collaboration in 2014. We begin this paper with an introduction of the XSEDE and PRACE organizations and the motivation for a collaborative effort between these two organizations. We then talk about the three projects that were involved in this collaborati...

Diabetic retinopathy (DR) remains the leading cause of visual loss in working age adults in the United States and other developed countries worldwide. Previous studies have reported hemodynamic changes in the diabetic eye that precede clinically evident pathological alterations of the retinal microvasculature. There exists a pressing need for new m...

The presentation of potentially pathogenic peptides by major histocompat-ibility complex (MHC) molecules is one of the most important processes in adaptive immune defense. Prediction of peptide − MHC (pMHC) binding affinities is therefore a principal objective of theoretical immunology. Machine learning techniques achieve good results if substantia...

Quantum chemistry is an important area of application for quantum computation. In particular, quantum algorithms applied to the electronic structure problem promise exact, efficient methods for determination of the electronic energy of atoms and molecules. The Bravyi–Kitaev transformation is a method of mapping the occupation state of a fermionic s...

[This corrects the article DOI: 10.1371/journal.pbio.1002125.].

Cerebrovascular diseases such as brain aneurysms are a primary cause of adult disability. The flow dynamics in brain arteries, both during periods of rest and increased activity, are known to be a major factor in the risk of aneurysm formation and rupture. The precise relation is however still an open field of investigation. We present an automated...

Author Summary The question of how blood vessel networks achieve their branching patterns is key to our understanding of organ formation as well as diseases that involve vascular anomalies. Regression (or pruning) of blood vessel segments is required for functional vascular branching patterns; however, the molecular basis for this is poorly underst...

Fibroblast growth factor receptors (FGFRs) are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray crys- tallography and biophysica...

Fibroblast growth factor receptors (FGFRs) are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray crystallography and biophysical...

Compared to proteins, the relationship between structure, dynamics and function of RNA enzymes (known as ribozymes) is far less well understood, despite the fact that ribozymes are found in many organisms and are often conceived as "molecular fossils" of the first self-replicating molecules to have arisen on Earth. To investigate how ribozymal func...

A quantitative description is presented of the dynamical process of polymer intercalation into clay tactoids and the ensuing aggregation of polymer-entangled tactoids into larger structures, obtaining various characteristics of these nanocomposites, including clay-layer spacings, out-of-plane clay-sheet bending energies, X-ray diffractograms, and m...

Near attack conformations (NACs) are conformations extending from the ground state (GS) that lie on the transition path of a chemical reaction. Here, we develop a method for computing the thermodynamic contribution to catalysis due to NAC formation in bimolecular reactions, within the limit of a classical molecular dynamics force field. We make use...

Secure access to patient data is becoming of increasing importance, as medical informatics grows in significance, to both assist with population health studies, and patient specific medicine in support of treatment. However, assembling the many different types of data emanating from the clinic is in itself a difficulty, and doing so across national...

Unlabelled: Infection with HIV-2 can ultimately lead to AIDS, although disease progression is much slower than with HIV-1. HIV-2 patients are mostly treated with a combination of nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and protease inhibitors designed for HIV-1. Many studies have described the development of HIV-1 resistance to NR...

Obtaining a good load balance is a significant challenge in scaling up lattice-Boltzmann simulations of realistic sparse problems to the exascale. Here we analyze the effect of weighted decomposition on the performance of the HemeLB lattice-Boltzmann simulation environment, when applied to sparse domains. Prior to domain decomposition, we assign wa...

The fabrication of novel soft materials is an important scientific and technological challenge. We investigate the response of magnetic ellipsoidal particles adsorbed at fluid-fluid interfaces to external magnetic fields. By exploiting previously discovered first-order orientation phase transitions we show how to switch on and off dipolar capillary...

We present the Multiscale Coupling Library and Environment: MUSCLE 2. This multiscale component-based execution environment has a simple to use Java, C++, C, Python and Fortran API, compatible with MPI, OpenMP and threading codes. We demonstrate its local and distributed computing capabilities and compare its performance to MUSCLE 1, file copy, MPI...

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject area...

We argue that, despite the fact that the field of multiscale modelling and simulation has enjoyed significant success within the past decade, it still holds many open questions that are deemed important but so far have barely been explored. We believe that this is at least in part due to the fact that the field has been mainly developed within disc...

Multiscale simulations model phenomena across natural scales using monolithic or component-based code, running on local or distributed resources. In this work, we investigate the performance of distributed multiscale computing of component-based models, guided by six multiscale applications with different characteristics and from several discipline...

Manufacturing new soft materials with specific optical, mechanical and magnetic properties is a significant challenge. Assembling and manipulating colloidal particles at fluid interfaces is a promising way to make such materials. We use lattice-Boltzmann simulations to investigate the response of magnetic ellipsoidal particles adsorbed at liquid-li...