Simone Melchionna

Hoover NPT dynamics for systems varying in shape and size

In this paper we write down equations of motion (following the approach pioneered by Hoover) for an exact isothermal-isobaric molecular dynamics simulation, and we extend them to multiple thermostating rates, to a shape-varying cell and to molecular systems, coherently with the previous ‘extended system method’. An integration scheme is proposed together with a numerical illustration of the method.

Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies

Simulations Complement Experimental Studies Jessica Nasica-Labouze,† Phuong H. Nguyen,† Fabio Sterpone,† Olivia Berthoumieu,‡ Nicolae-Viorel Buchete, Sebastien Cote, Alfonso De Simone, Andrew J. Doig, Peter Faller,‡ Angel Garcia, Alessandro Laio, Mai Suan Li, Simone Melchionna, Normand Mousseau, Yuguang Mu, Anant Paravastu, Samuela Pasquali,† David J. Rosenman, Birgit Strodel, Bogdan Tarus,† John H. Viles, Tong Zhang,†,▲ Chunyu Wang, and Philippe Derreumaux*,†,□ †Laboratoire de Biochimie Theorique, Institut de Biologie Physico-Chimique (IBPC), UPR9080 CNRS, Universite Paris Diderot, Sorbonne Paris Cite, 13 rue Pierre et Marie Curie, 75005 Paris, France ‡LCC (Laboratoire de Chimie de Coordination), CNRS, Universite de Toulouse, Universite Paul Sabatier (UPS), Institut National Polytechnique de Toulouse (INPT), 205 route de Narbonne, BP 44099, Toulouse F-31077 Cedex 4, France School of Physics & Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4, Ireland Deṕartement de Physique and Groupe de recherche sur les proteines membranaires (GEPROM), Universite de Montreal, C.P. 6128, succursale Centre-ville, Montreal, Quebec H3C 3T5, Canada Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom Department of Physics, Applied Physics, & Astronomy, and Department of Biology, Rensselaer Polytechnic Institute, Troy, New York 12180, United States The International School for Advanced Studies (SISSA), Via Bonomea 265, 34136 Trieste, Italy Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw, Poland Institute for Computational Science and Technology, SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam Instituto Processi Chimico-Fisici, CNR-IPCF, Consiglio Nazionale delle Ricerche, 00185 Roma, Italy School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore Department of Chemical and Biomedical Engineering, Florida A&M University-Florida State University (FAMU-FSU) College of Engineering, 2525 Pottsdamer Street, Tallahassee, Florida 32310, United States National High Magnetic Field Laboratory, 1800 East Paul Dirac Drive, Tallahassee, Florida 32310, United States Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Julich GmbH, 52425 Julich, Germany School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom Institut Universitaire de France, 75005 Paris, France

Intermittent permeation of cylindrical nanopores by water.

Molecular-dynamics simulations of water molecules in nanometer sized cylindrical channels connecting two reservoirs show that the permeation of water is very sensitive to the channel radius and to electric polarization of the embedding material. At threshold, the permeation is intermittent on a nanosecond time scale, and strongly enhanced by the presence of an ion inside the channel, providing a possible mechanism for gating. Confined water remains surprisingly fluid and bulklike. Its behavior differs strikingly from that of a reference Lennard-Jones fluid, which tends to contract into a highly layered structure inside the channel.

Multiscale Coupling of Molecular Dynamics and Hydrodynamics: Application to DNA Translocation through a Nanopore

We present a multiscale approach to the modeling of polymer dynamics in the presence of a fluid solvent. The approach combines Langevin molecular dynamics (MD) techniques with a mesoscopic lattice Boltzmann (LB) method for the solvent dynamics. A unique feature of the present approach is that hydrodynamic interactions between the solute macromolecule and the aqueous solvent are handled explicitly, and yet in a computationally tractable way due to the dual particle‐field nature of the LB solver. The suitability of the present LB‐MD multiscale approach is demonstrated for the problem of polymer fast translocation through a nanopore. We also provide an interpretation of our results in the context of DNA translocation through a nanopore, a problem that has attracted much theoretical and experimental attention recently.

MUPHY: A parallel MUlti PHYsics/scale code for high performance bio-fluidic simulations

We present a parallel version of MUPHY, a multi-physics/scale code based upon the combination of microscopic Molecular Dynamics (MD) with a hydro-kinetic Lattice Boltzmann (LB) method. The features of the parallel version of MUPHY are hereby demonstrated for the case of translocation of biopolymers through nanometer-sized, multi-pore configurations, taking into explicit account the hydrodynamic interactions of the translocating molecules with the surrounding fluid. The parallel implementation exhibits excellent scalability on the IBM BlueGene platform and includes techniques which may improve the flexibility and efficiency of other complex multi-physics parallel applications, such as hemodynamics, targeted-drug delivery and others.

Evaluation of Artery Visualizations for Heart Disease Diagnosis

Heart disease is the number one killer in the United States, and finding indicators of the disease at an early stage is critical for treatment and prevention. In this paper we evaluate visualization techniques that enable the diagnosis of coronary artery disease. A key physical quantity of medical interest is endothelial shear stress (ESS). Low ESS has been associated with sites of lesion formation and rapid progression of disease in the coronary arteries. Having effective visualizations of a patients ESS data is vital for the quick and thorough non-invasive evaluation by a cardiologist. We present a task taxonomy for hemodynamics based on a formative user study with domain experts. Based on the results of this study we developed HemoVis, an interactive visualization application for heart disease diagnosis that uses a novel 2D tree diagram representation of coronary artery trees. We present the results of a formal quantitative user study with domain experts that evaluates the effect of 2D versus 3D artery representations and of color maps on identifying regions of low ESS. We show statistically significant results demonstrating that our 2D visualizations are more accurate and efficient than 3D representations, and that a perceptually appropriate color map leads to fewer diagnostic mistakes than a rainbow color map.

Molecular dynamics investigation of water permeation through nanopores

Molecular dynamics (MD) simulations are carried out to investigate the permeation of nanometer-sized cylindrical pores connecting two reservoirs, by water molecules and by a reference Lennard-Jones fluid. Water molecules penetrate a channel of fixed length only beyond a minimum radius. Near threshold, permeation is found to be intermittent and sensitive to other physical parameters, including the polarizability of the medium (e.g., a cell membrane) embedding the channel. Once the molecules fill the pore, the confined water exhibits properties (mean density, diffusivity, hydrogen bonding) surprisingly close to those of the bulk. The intermittent behavior near the threshold is analyzed in terms of a Landau-like grand potential regarded as a function of the pore occupancy. The grand potential, which is determined using a biased sampling technique, generally exhibits two minima, associated with the “empty” and “filled” states, separated by a potential barrier (transition state). No intermittent filling of ide...

The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems

The OPEP coarse-grained protein model has been applied to a wide range of applications since its first release 15 years ago. The model, which combines energetic and structural accuracy and chemical specificity, allows the study of single protein properties, DNA-RNA complexes, amyloid fibril formation and protein suspensions in a crowded environment. Here we first review the current state of the model and the most exciting applications using advanced conformational sampling methods. We then present the current limitations and a perspective on the ongoing developments.

Hydrodynamic correlations in the translocation of a biopolymer through a nanopore : Theory and multiscale simulations

We investigate the process of biopolymer translocation through a narrow pore using a multiscale approach which explicitly accounts for the hydrodynamic interactions of the molecule with the surrounding solvent. The simulations confirm that the coupling of the correlated molecular motion to hydrodynamics results in significant acceleration of the translocation process. Based on these results, we construct a phenomenological model which incorporates the statistical and dynamical features of the translocation process and predicts a power-law dependence of the translocation time on the polymer length with an exponent alpha approximately 1.2. The actual value of the exponent from the simulations is alpha=1.28+/-0.01, which is in excellent agreement with experimental measurements of DNA translocation through a nanopore, and is not sensitive to the choice of parameters in the simulation. The mechanism behind the emergence of such a robust exponent is related to the interplay between the longitudinal and transversal dynamics of both translocated and untranslocated segments. The connection to the macroscopic picture involves separating the contributions from the blob shrinking and shifting processes, which are both essential to the translocation dynamics.

Prediction of coronary artery plaque progression and potential rupture from 320-detector row prospectively ECG-gated single heart beat CT angiography: Lattice Boltzmann evaluation of endothelial shear stress

Advances in MDCT will extend coronary CTA beyond the morphology data provided by systems that use 64 or fewer detector rows. Newer coronary CTA technology such as prospective ECG-gating will also enable lower dose examinations. Since the current standard of care for coronary diagnoses is catheterization, CT will continue to be benchmarked against catheterization reference points, in particular temporal resolution, spatial resolution, radiation dose, and volume coverage. This article focuses on single heart beat cardiac acquisitions enabled by 320-detector row CT. Imaging with this system can now be performed with patient radiation doses comparable to catheterization. The high image quality, excellent contrast opacification, and absence of stair-step artifact provide the potential to evaluate endothelial shear stress (ESS) noninvasively with CT. Low ESS is known to lead to the development and progression of atherosclerotic plaque culminating in high-risk vulnerable plaque likely to rupture and cause an acute coronary event. The magnitude of local low ESS, in combination with the local remodeling response and the severity of systemic risk factors, determines the natural history of each plaque. This paper describes the steps required to derive an ESS map from 320-detector row CT data using the Lattice Boltzmann method to include the complex geometry of the coronary arterial tree. This approach diminishes the limitations of other computational fluid dynamics methods to properly evaluate multiple coronary arteries, including the complex geometry of coronary bifurcations where lesions tend to develop.