Search results for "molecular dynamics"
showing 10 items of 1075 documents
Dynamic-shared Pharmacophore Approach as Tool to Design New Allosteric PRC2 Inhibitors, Targeting EED Binding Pocket.
2020
Abstract: The Polycomb Repressive complex 2 (PRC2) maintains a repressive chromatin state and silences many genes, acting as methylase on histone tails. This enzyme was found overexpressed in many types of cancer. In this work, we have set up a Computer-Aided Drug Design approach based on the allosteric modulation of PRC2. In order to minimize the possible bias derived from using a single set of coordinates within the protein-ligand complex, a dynamic workflow was developed. In details, molecular dynamic was used as tool to identify the most significant ligand-protein interactions from several crystallized protein structures. The identified features were used for the creation of dynamic pha…
An omics perspective to the molecular mechanisms of anticancer metallo-drugs in the computational microscope era
2017
Introduction: Metallo-drugs have attracted enormous interest for cancer treatment. The achievements of this drug-type are summarized by the success story of cisplatin. That being said, there have been many drawbacks with its clinical use, which prompted decades worth of research efforts to move towards safer and more effective agents, either containing platinum or different metals. Areas covered: In this review, the authors provide an atomistic picture of the molecular mechanisms involving selected metallo-drugs from structural and molecular simulation studies. They also provide an omics perspective, pointing out many unsettled aspects of the most relevant families of metallo-drugs at an ep…
Non-equilibrium Markov state modeling of periodically driven biomolecules
2019
Molecular dynamics simulations allow to study the structure and dynamics of single biomolecules in microscopic detail. However, many processes occur on time scales beyond the reach of fully atomistic simulations and require coarse-grained multiscale models. While systematic approaches to construct such models have become available, these typically rely on microscopic dynamics that obey detailed balance. In vivo, however, biomolecules are constantly driven away from equilibrium in order to perform specific functions and thus break detailed balance. Here we introduce a method to construct Markov state models for systems that are driven through periodically changing one (or several) external p…
GROMEX: A Scalable and Versatile Fast Multipole Method for Biomolecular Simulation
2020
Atomistic simulations of large biomolecular systems with chemical variability such as constant pH dynamic protonation offer multiple challenges in high performance computing. One of them is the correct treatment of the involved electrostatics in an efficient and highly scalable way. Here we review and assess two of the main building blocks that will permit such simulations: (1) An electrostatics library based on the Fast Multipole Method (FMM) that treats local alternative charge distributions with minimal overhead, and (2) A $λ$-dynamics module working in tandem with the FMM that enables various types of chemical transitions during the simulation. Our $λ$-dynamics and FMM implementations d…
Concurrent Molecular Dynamics Simulation of ST2 Water on a Transputer Array
1988
Abstract A concurrent implementation of a Molecular Dynamics program for ST2 water molecules is presented, which exploits the great potentialities of the Transputer arrays for statistical mechanical calculations. High load-balance efficiency is obtained using a new task decomposition algorithm which evenly distributes particles and interaction calculations among the processors. This approach can also help to solve efficiently the more general problem of task distribution in parallel computing of symmetric pairwise system properties.
Molecular dynamics simulations in hybrid particle-continuum schemes: Pitfalls and caveats
2017
Heterogeneous multiscale methods (HMM) combine molecular accuracy of particle-based simulations with the computational efficiency of continuum descriptions to model flow in soft matter liquids. In these schemes, molecular simulations typically pose a computational bottleneck, which we investigate in detail in this study. We find that it is preferable to simulate many small systems as opposed to a few large systems, and that a choice of a simple isokinetic thermostat is typically sufficient while thermostats such as Lowe-Andersen allow for simulations at elevated viscosity. We discuss suitable choices for time steps and finite-size effects which arise in the limit of very small simulation bo…
Investigating the cooling rate dependence of amorphous silica: A computer simulation study
1996
We use molecular dynamics computer simulations to study the dependence of the properties of amorphous silica on the cooling rate with which the glass has been produced. In particular we show that the density, the glass transition temperature, the radial distribution function and the distribution of the size of the rings depend on the cooling rate.
Realistic Implementation of the Particle Model for the Visualization of Nanoparticle Precipitation and Growth
2019
An application for visualizing the aggregation of structureless atoms is presented. The application allows us to demonstrate on a qualitative basis, as well as by quantitatively monitoring the aggregate surface/volume ratio, that the enhanced reactivity of nanoparticles can be connected with their large specific surface. It is suggested that, along with the use of geometric analogies, this bottom-up approach can be effective in discussing the enhanced reactivity proprieties of nanoparticles. The application is based on a two-dimensional realistic dynamic model where atoms move because of their thermal and interaction potential energies, and the trajectories are determined by solving numeric…
Structure and transport properties of amorphous aluminium silicates: computer simulation studies
2005
The structure and transport properties of SiO2-Al2O3 melts containing 13 mol% and 47 mol% Al2O3 are investigated by means of large scale molecular dynamics computer simulations. The interactions between the atoms are modelled by a pair potential which is a modified version of the one proposed by Kramer et al. [J. Am. Chem. Soc. 64, 6435 (1991)]. Fully equilibrated melts in the temperature range 6000 K >= T > 2000 K are considered as well as glass configurations, that were obtained by a rapid quench from the lowest melt temperatures. Each system is simulated at two different densities in order to study the effect of pressure on structural and dynamic properties. We find that the Al ato…
Thermal Expansion in Small Metal Clusters and its Impact on the Electric Polarizability
2000
The thermal expansion coefficients of $\mathrm{Na}_{N}$ clusters with $8 \le N \le 40$ and $\mathrm{Al}_{7}$, $\mathrm{Al}_{13}^-$ and $\mathrm{Al}_{14}^-$ are obtained from {\it ab initio} Born-Oppenheimer LDA molecular dynamics. Thermal expansion of small metal clusters is considerably larger than that in the bulk and size-dependent. We demonstrate that the average static electric dipole polarizability of Na clusters depends linearly on the mean interatomic distance and only to a minor extent on the detailed ionic configuration when the overall shape of the electron density is enforced by electronic shell effects. The polarizability is thus a sensitive indicator for thermal expansion. We …