Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Fast parallel algorithms for short-range molecular dynamics

A theoretical perspective is provided on the glass transition in molecular liquids at thermal equilibrium, on the spatially heterogeneous and aging dynamics of disordered materials, and on the rheology of soft glassy materials. We start with a broad introduction to the field and emphasize its connections with other subjects and its relevance. The important role played by computer simulations in studying and understanding the dynamics of systems close to the glass transition at the molecular level is given. The recent progress on the subject of the spatially heterogeneous dynamics that characterizes structural relaxation in materials with slow dynamics is reviewed. The main theoretical approaches are presented describing the glass transition in supercooled liquids, focusing on theories that have a microscopic, statistical mechanics basis. We describe both successes and failures and critically assess the current status of each of these approaches. The physics of aging dynamics in disordered materials and the rheology of soft glassy materials are then discussed, and recent theoretical progress is described. For each section, an extensive overview is given of the most recent advances, but we also describe in some detail the important open problems that will occupy a central place in this field in the coming years.

Theoretical perspective on the glass transition and amorphous materials

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Strategies to Address Low Drug Solubility in Discovery and Development

A review of nonlinear oscillatory shear tests: Analysis and application of large amplitude oscillatory shear (LAOS)

Basic characteristics of the liquid-glass transition are reviewed, emphasizing its universality and briefly summarizing the most popular phenomenological models. Discussion is focused on a number of alternative models which one way or the other connect the fast and slow degrees of freedom of viscous liquids. It is shown that all these ``elastic'' models are equivalent in the simplest approximation.

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Colloquium : The glass transition and elastic models of glass-forming liquids

For glass-forming substances, we show that the ratio ${E}_{\ensuremath{\beta}}{/RT}_{g}$ can be predicted quantitatively from the coupling model. Here ${E}_{\ensuremath{\beta}}$ is the glassy state activation enthalpy of the Johari-Goldstein \ensuremath{\beta} relaxation, ${T}_{g}$ is the glass transition temperature of the \ensuremath{\alpha} relaxation, and R is the gas constant. The calculated value is in good agreement with the experimental value in many glass formers. The results locate the origin of this cross correlation between ${E}_{\ensuremath{\beta}}$ of the Johari-Goldstein \ensuremath{\beta} relaxation and ${T}_{g}$ of the \ensuremath{\alpha} relaxation, although there are some notable exceptions to this cross correlation.

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Relation between the activation energy of the Johari-Goldstein β relaxation and T g of glass formers

Upon decreasing temperature or increasing pressure, a noncrystallizing liquid will vitrify; that is, the structural relaxation time, τα, becomes so long that the system cannot attain an equilibrium configuration in the available time. Theories, including the well-known free volume and configurational entropy models, explain the glass transition by invoking a single quantity that governs the structural relaxation time. The dispersion of the structural relaxation (i.e., the structural relaxation function) is either not addressed or is derived as a parallel consequence (or afterthought) and thus is independent of τα. In these models the time dependence of the relaxation bears no fundamental relationship to the value of τα or other dynamic properties. Such approaches appear to be incompatible with a general experimental fact recently discovered in glass-formers:  for a given material at a fixed value of τα, the dispersion is constant, independent of thermodynamic conditions (T and P); that is, the shape of th...

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Do theories of the glass transition, in which the structural relaxation time does not define the dispersion of the structural relaxation, need revision?

Most glass-forming systems are composed of basic units interacting with each other with a nontrivial anharmonic potential. Naturally, relaxation and diffusion in glass formers is a many-body problem. Results from recent experimental studies are presented to show the effects of many-body relaxation and diffusion manifested on the dynamic properties of glass formers. Considering that the effects are general and critical, the problem of glass transition will not be solved until the many-body nature of the relaxation process has been incorporated fundamentally into any theory.

Many-Body Nature of Relaxation Processes in Glass-Forming Systems.

There is a plethora of experimental data on the dynamics of water in mixtures with glycerol, ethylene glycol, ethylene glycol oligomers, poly(ethylene glycol) 400 and 600, propanol, poly(vinyl pyrr...

The Johari-Goldstein beta-relaxation of water.

When a liquid is cooled below its melting temperature, if crystallization is avoided, it forms a glass. This phenomenon, called glass transition, is characterized by a marked increase of viscosity, about 14 orders of magnitude, in a narrow temperature interval. The microscopic mechanism behind the glass transition is still poorly understood. However, recently, great advances have been made in the identification of cooperative rearranging regions, or dynamical heterogeneities, i.e., domains of the liquid whose relaxation is highly correlated. The growth of the size of these domains is now believed to be the driving mechanism for the increase of the viscosity. Recently a tool to quantify the size of these domains has been proposed. We apply this tool to a wide class of materials to investigate the correlation between the size of the heterogeneities and their configurational entropy, i.e., the number of states accessible to a correlated domain. We find that the relaxation time of a given system, apart from a material dependent prefactor, is a universal function of the configurational entropy of a correlated domain. As a consequence, we find that, at the glass transition temperature, the size of the domains and the configurational entropy per unit volume are anticorrelated, as originally predicted by the Adam-Gibbs theory. Finally, we use our data to extract some exponents defined in the framework of the random first-order theory, a recent quantitative theory of the glass transition.

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Simone Capaccioli

Papers

Relation between the activation energy of the Johari-Goldstein β relaxation and T g of glass formers

Do theories of the glass transition, in which the structural relaxation time does not define the dispersion of the structural relaxation, need revision?

Many-Body Nature of Relaxation Processes in Glass-Forming Systems.

The Johari-Goldstein beta-relaxation of water.

Dynamically correlated regions and configurational entropy in supercooled liquids