Peter Coveney

Peter Coveney
  • University College London

About

499
Publications
62,671
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18,660
Citations
Current institution
University College London

Publications

Publications (499)
Article
Full-text available
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...
Article
Full-text available
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...
Preprint
Full-text available
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...
Preprint
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Preprint
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Preprint
Full-text available
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...
Article
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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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...
Preprint
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...
Preprint
Full-text available
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...
Article
Full-text available
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...
Article
"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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
T lymphocytes are stimulated when they recognize 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 (TCR) molecules together with both the peptides and MHC proteins they bind to, it has been difficult to design vaccines and treatments base...
Article
Full-text available
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...
Article
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...
Article
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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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
Article
Full-text available
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...
Article
Full-text available
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,...
Article
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...
Article
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...
Article
Full-text available
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...
Preprint
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Conference Paper
Full-text available
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...
Conference Paper
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...
Article
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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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...
Conference Paper
Full-text available
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...
Article
Full-text available
There is currently limited understanding of the role played by haemodynamic forces on the processes governing vascular development. One of many obstacles to be overcome is being able to measure those forces, at the required resolution level, on vessels only a few micrometres thick. In the current paper, we present an in silico method for the comput...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
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...
Article
Full-text available
The energy required to detach a single particle from a fluid-fluid interface is an important parameter for designing certain soft materials, for example, emulsions stabilised by colloidal particles, colloidosomes designed for targeted drug delivery, and bio-sensors composed of magnetic particles adsorbed at interfaces. For a fixed particle volume,...
Article
Full-text available
We show, via three-dimensional immersed-boundary-finite-element-lattice-Boltzmann simulations, that deformability-based red blood cell (RBC) separation in deterministic lateral displacement (DLD) devices is possible. This is due to the deformability-dependent lateral extension of RBCs and enables us to predict a priori which RBCs will be displaced...
Article
Full-text available
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...
Article
Full-text available
The translocation of nucleotide molecules across biological and synthetic nanopores has attracted attention as a next generation technique for sequencing DNA. Computer simulations have the ability to provide atomistic-level insight into important states and processes, delivering a means to develop a fundamental understanding of the translocation ev...
Article
The use of molecular simulation to estimate the strength of macromolecular binding free energies is becoming increasingly widespread, with goals ranging from lead optimization and enrichment in drug discovery to personalizing or stratifying treatment regimes. In order to realize the potential of such approaches to predict new results, not merely to...
Conference Paper
The virtual human concept is a compelling one, offering an in silico environment within which truly personalised medicine can be implemented, taking into account the specific features of every one of us as an individual, from our personal genome to the anatomy of our connected organ systems. Such virtual humans will not only support medical and cli...
Conference Paper
Full-text available
Cerebral aneurysms are one of the prevalent and devastating cerebrovascular diseases of adult population worldwide. In most cases, it causes rupturing of cerebral vessels inside the brain, which leads to subarachnoid hemorrhage. In this work, we present a clinical workflow model to assist endovascular interventionists to select the type of stent-re...
Data
Additional Supporting Information may be found in the online version of this article.
Conference Paper
Full-text available
DECI (Distributed European Computing Initiative) is a resource exchange programme which provides researchers all over Europe with access to Tier-1 super-computing resources. DECI first ran within the DEISA project but since mid-2011 has operated within the PRACE environment (http://www.prace-project.eu) , so far supporting 99 projects providing app...
Article
Computer simulation is finding a role in an increasing number of scientific disciplines, concomitant with the rise in available computing power. Marshalling this power facilitates new, more effective and different research than has been hitherto possible. Realizing this inevitably requires access to computational power beyond the desktop, making us...
Article
Full-text available
We present a reusable solution that supports users in combining single-scale models to create a multiscale application. Our approach applies several multiscale programming tools to allow users to compose multiscale applications using a graphical interface, and provides an easy way to execute these multiscale applications on international production...
Article
Full-text available
We study the behaviour of cubic blue phases under shear flow via lattice Boltzmann simulations. We focus on the two experimentally observed phases, Blue Phase I (BPI) and Blue Phase II (BPII). The disclination network of Blue Phase II continuously breaks and reforms under steady shear, leading to an oscillatory stress response in time. For larger s...
Article
The human histone deacetylase 8 (HDAC8) is a key hydrolase in gene regulation and has been identified as a drug target for the treatment of several cancers. Previously the HDAC8 enzyme has been extensively studied using biochemical techniques, x-ray crystallography, and computational methods. Those investigations have yielded detailed information a...
Article
Full-text available
Reverse transcriptase (RT) plays an essential role in HIV-1 replication, and inhibition of this enzyme is a key component of HIV-treatment. However, the use of RT inhibitors can lead to the emergence of drug-resistant variants. Until recently, most clinically relevant resistance mutations were found in the polymerase domain of RT. Lately, an increa...
Article
The voltage-driven passage of biological polymers through nanoscale pores is an analytically, technologically, and biologically relevant process. Despite various studies on homopolymer translocation there are still several open questions on the fundamental aspects of the pore transport. One of the most important unresolved issues revolves around th...
Data
Full-text available
The distribution of virion maturation times from 10,000 simulations with random parameter sets. (PDF)
Data
Full-text available
Adding an initial inoculum of mature protease results in modest decrease in VMT. (PDF)
Data
Full-text available
The time course of simulated Gag and Gag-Pol processing, using kinetic rate constants estimated based on full-length Gag cleavage. (A) Virus maturation time (VMT) (dashed red line in all panels) is still triggered by the decay of the CA.SP1 fragment (blue line; threshold of trans-dominant inhibition of particle maturation indicated by dashed horizo...
Data
Estimation of catalytic rate constants. (PDF)
Data
Full-text available
The effect of single parameter variation on VMT using an alternative set of kinetic rate constants. (PDF)
Data
The time course of the major intermediates of simulated Gag (A) and Gag-Pol (B) processing. (PDF)
Data
Compensation of virion maturation time (VMT) with different time courses of reaction products. (PDF)
Data
Full-text available
Half-normalized local sensitivity functions of the concentration of CA.SP1 with respect to selected parameters. (PDF)
Data
Computer code of simulations. (ZIP)
Data
The size of the critical subset of PR or Gag-Pol dimers as a function of VMT required for viability. Simulations were run with different concentrations of two types of inhibitors binding either to mature PR (red symbols) or to full-length Gag-Pol dimers (blue symbols). The binding rate constants of both PIs were parameterized with data estimated fo...
Article
Full-text available
Proteolytic processing of Gag and Gag-Pol polyproteins by the viral protease (PR) is crucial for the production of infectious HIV-1, and inhibitors of the viral PR are an integral part of current antiretroviral therapy. The process has several layers of complexity (multiple cleavage sites and substrates; multiple enzyme forms; PR auto-processing),...
Article
Full-text available
The EUDAT project is a pan-European data initiative that started in October 2011. The project brings together a unique consortium of 25 partners – including research communities, national data and high performance computing (HPC) centres, technology providers, and funding agencies – from 13 countries. EUDAT aims to build a sustainable cross-discipl...
Patent
The present invention relates to a water-based wellbore fluid comprising water, a hydration inhibitor including a hydroxyalkyl polysaccharide with a weight average molar mass of less than 5,000 and at least one other component selected from the group comprising a rheology modifier, fluid loss control agent, inorganic or organic salt, dispersant and...
Article
Full-text available
European funding under Framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for 5 years. The VPH Network of Excellence (NoE) has been set up to help develop common standards, open source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It...

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