Parallelization of the algorithm WHAM with NVIDIA CUDA.

The aim of my thesis is to parallelize the Weighting Histogram Analysis Method (WHAM), which is a popular algorithm used to calculate the Free Energy of a molucular system in Molecular Dynamics simulations. WHAM works in post processing in cooperation with another algorithm called Umbrella Sampling. Umbrella Sampling has the purpose to add a biasing in the potential energy of the system in order to force the system to sample a specific region in the configurational space. Several N independent simulations are performed in order to sample all the region of interest. Subsequently, the WHAM algorithm is used to estimate the original system energy starting from the N atomic trajectories. The parallelization of WHAM has been performed through CUDA, a language that allows to work in GPUs of NVIDIA graphic cards, which have a parallel achitecture. The parallel implementation may sensibly speed up the WHAM execution compared to previous serial CPU imlementations. However, the WHAM CPU code presents some temporal criticalities to very high numbers of interactions. The algorithm has been written in C++ and executed in UNIX systems provided with NVIDIA graphic cards. The results were satisfying obtaining an increase of performances when the model was executed on graphics cards with compute capability greater. Nonetheless, the GPUs used to test the algorithm is quite old and not designated for scientific calculations. It is likely that a further performance increase will be obtained if the algorithm would be executed in clusters of GPU at high level of computational efficiency. The thesis is organized in the following way: I will first describe the mathematical formulation of Umbrella Sampling and WHAM algorithm with their apllications in the study of ionic channels and in Molecular Docking (Chapter 1); then, I will present the CUDA architectures used to implement the model (Chapter 2); and finally, the results obtained on model systems will be presented (Chapter 3).

Mode-specific chemisorption of CH4 on Pt{110}-(1 x 2) explored by first-principles molecular dynamics

The chemisorption of CH4 on Pt{110}-(1 x 2) has been studied by vibrational analysis of the reaction pathway defined by the potential energy surface and, in time reversal, by first-principles molecular dynamics simulations of CH4 associative desorption, with the electronic structure treated explicitly using density functional theory. We find that the symmetric stretch vibration ν1 is strongly coupled to the reaction coordinate; our results therefore provide a firm theoretical basis for recently reported state-resolved reactivity measurements, which show that excitation of the ν1 normal mode is the most efficient way to enhance the reaction probability

A Molecular Dynamics Study of the Early Stages of Calcium Carbonate Growth

<p>The precipitation of calcium carbonate in water has been examined using a combination of molecular dynamics and umbrella sampling. During 20 ns molecular dynamics trajectories at elevated calcium carbonate concentrations, amorphous particles are observed to form and appear to be composed of misaligned domains of vaterite and aragonite. The addition of further calcium ions to these clusters is found to be energetically favorable and virtually barrierless. By contrast, there is a large barrier to the addition of calcium to small calcite crystals. Thus, even though calcite nanocrystals are stable in solution, at high supersaturations, particles of amorphous material form because this material grows much faster than ordered calcite nanocrystals.</p>

Molecular dynamics simulations on parallel and antiparallel C.G*G triplexes

Molecular dynamics (MD) studies have been carried out on the Hoogsteen hydrogen bonded parallel and the reverse Hoogsteen hydrogen banded antiparallel C.G*G triplexes. Earlier, the molecular mechanics studies had shown that the parallel structure was energetically more favourable than the antiparallel structure. To characterize the structural stability of the two triplexes and to investigate whether the antiparallel structure can transit to an energetically more favourable structure, due to the local fluctuations in the structure during the MD simulation, the two structures were subjected to 200ps of constant temperature vacuum MD simulations at 300K. Initially no constraints were applied to the structures and it was observed that for the antiparallel tripler, the structure showed a large root mean square deviation from the starting structure within the first 12ps and the N4-H41-O6 hydrogen bond in the WC duplex got distorted due to a high propeller twist and a moderate increase in the opening angle in the basepairs. Starting from an initial value of 30 degrees, helical twist of the average structure from this simulation had a value of 36 degrees, while the parallel structure stabilized at a twist of 33 degrees. In spite of the hydrogen bond distortions in the antiparallel tripler, it was energetically comparable to the parallel tripler. To examine the structural characteristics of an undistorted structure, another MD simulation was performed on the antiparallel tripler by constraining all the hydrogen bonds. This structure stabilized at an average twist of 33 degrees. In the course of the dynamics though the energy of the molecule - compared to the initial structure - improved, it did not become comparable to the parallel structure. Energy minimization studies performed in the presence of explicit water and counterions also showed the two structures to be equally favourable energetically Together these results indicate that the parallel C.G*G tripler with Hoogsteen hydrogen bonds also represents a stereochemically and energetically favourable structure for this class of triplexes.

Molecular dynamics simulations of PPI dendrimer-drug complexes

Dendrimeric nanoparticles are potential drug delivery devices which can enhance the solubility of hydrophobic drugs, thus increasing their bioavailability and sustained release action. A quantitative understanding of the dendrimer-drug interactions can give valuable insight into the solubility and release profile of hydrophobic drug molecules in various solvent conditions. Fully atomistic molecular dynamics (MD) simulations have been performed to study the interactions of G5 PPIEDA (G5 ethylenediamine cored poly(propylene imine)) dendrimer and two well known drugs (Famotidine and Indomethacin) at different pH conditions. The study suggested that at low pH the dendrimer-drug complexes are thermodynamically unstable as compared to neutral and high pH conditions. Calculated Potential of Mean Force (PMF) by umbrella sampling showed that the release of drugs from the dendrimer at low pH is spontaneous, median release at neutral pH and slow release at high pH. In addition, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) binding free energy calculations were also performed at each umbrella sampling window to identify the various energy contributions. To understand the effect of dendrimer chemistry and topology on the solubility and release profile of drugs, this study is extended to explore the solubility and release profile of phenylbutazone drug complexed with G3 poly(amidoamine) and G4 diaminobutane cored PPI dendrimers. The results indicate that the pH-induced conformational changes in dendrimer, ionization states, dendrimer type and pK(a) of the guest molecules influence the free energy barrier and stability of complexation, and thus regulate drug loading, solubility and release.

Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating pK(a) Values from Metadynamics Sampling

Changes in the protonation and deprotonation of amino acid residues in proteins play a key role in many biological processes and pathways. Here, we report calculations of the free-energy profile for the protonation deprotonation reaction of the 20 canonical alpha amino acids in aqueous solutions using ab initio Car-Parrinello molecular dynamics simulations coupled with metad-ynamics sampling. We show here that the calculated change in free energy of the dissociation reaction provides estimates of the multiple pK(a) values of the amino acids that are in good agreement with experiment. We use the bond-length-dependent number of the protons coordinated to the hydroxyl oxygen of the carboxylic and the amine groups as the collective variables to explore the free-energy profiles of the Bronsted acid-base chemistry of amino acids in aqueous solutions. We ensure that the amino acid undergoing dissociation is solvated by at least three hydrations shells with all water molecules included in the simulations. The method works equally well for amino acids with neutral, acidic and basic side chains and provides estimates of the multiple pK(a) values with a mean relative error, with respect to experimental results, of 0.2 pK(a) units.

Study on structure and molecular dynamics of starch/poly(sodium acrylate)grafted superabsorbent by C-13 solid state NMR

The domain-structure of samples containing a series of starch/poly(sodium acrylate)-grafted superabsorbents, pure starch, pure poly(sodium acrylate), and blend of starch/poly(sodium acrylate) has been studied by high-resolution solid-state C-13 NMR spectroscopy at room temperature. The result shows that the crystallinity of starch decreases greatly in the grafted and blended samples.

Molecular dynamics simulation of observed c(4x4) and c(4x3) C60 alignments on the Si(100) reconstructed surface.

We have implemented a large-scale classical molecular dynamics simulation at constant temperature to provide a theoretical insight into the results of a recently performed experiment on the monolayer and multi-layer formations of molecular films on the Si(100) reconstructed dimerized surface. Our simulation has successfully reproduced all of the morphologies observed on the monolayer film by this experiment. We have obtained the formation of both c(4 4) and c(4 3) structures of the molecules and have also obtained phase transitions of the former into the latter.

Molecular dynamics simulation of nanoindentation of Fe₃C and tetrahedral Fe₄C

Study of nanomechanical response of iron carbides is important because presence of iron carbides greatly influences the performance and longevity of steel components. This work contributes to the literature by exploring nanoindentation of nanocrystalline Fe3C and tetrahedral-Fe4C using molecular dynamics simulation. The chemical interactions of iron and carbon were described through an analytical bond order inter-atomic potential (ABOP) energy function. The indentations were performed at an indentation speed of 50 m/sec and a repeat trial was performed at 5 m/sec. Load-displacement (P-h) curve for both these carbides showed residual indentation depth and maximum indentation depth (hf/hmax) ratio to be higher than 0.7 i.e. a circumstance where Oliver and Pharr method was not appropriate to be applied to evaluate the material properties. Alternate evaluation revealed Fe3C to be much harder than Fe4C. Gibbs free energy of formation and radial distribution function, coupled with state of the average local temperature and von Mises stresses indicate the formation of a new phase of iron-carbide. Formation of this newer phase was found to be due to deviatoric strain rather than the high temperature induced in the substrate during nanoindentation<br/>

The effects of anticalcification treatments and hydration on the molecular dynamics of bovine pericardium collagen as revealed by (13)C solid-state NMR

This article describes a solid-state NMR (SSNMR) investigation of the influence of hydration and chemical cross-linking on the molecular dynamics of the constituents of the bovine pericardium (BP) tissues and its relation to the mechanical properties of the tissue. Samples of natural phenetylamine-diepoxide (DE)- and glutaraldehyde (GL)-fixed BP were investigated by (13)C cross-polarization SSNMR to probe the dynamics of the collagen, and the results were correlated to the mechanical properties of the tissues, probed by dynamical mechanical analysis. For samples of natural BP, the NMR results show that the higher the hydration level the more pronounced the molecular dynamics of the collagen backbone and sidechains, decreasing the tissue`s elastic modulus. In contrast, in DE- and GL-treated samples, the collagen molecules are more rigid, and the hydration seems to be less effective in increasing the collagen molecular dynamics and reducing the mechanical strength of the samples. This is mostly attributed to the presence of cross-links between the collagen plates, which renders the collagen mobility less dependent on the water absorption in chemically treated samples. Copyright (C) 2010 John Wiley & Sons, Ltd.

Structure and thermodynamics of H3O+(H2O)8 clusters: A combined molecular dynamics and quantum mechanics approach

We have studied the structure and stability of (H3O+)(H2O)8 clusters using a combination of molecular dynamics sampling and high-level ab initio calculations. 20 distinct oxygen frameworks are found within 2 kcal/mol of the electronic or standard Gibbs free energy minimum. The impact of quantum zero-point vibrational corrections on the relative stability of these isomers is quite significant. The box-like isomers are favored in terms of electronic energy, but with the inclusion of zero-point vibrational corrections and entropic effects tree-like isomers are favored at higher temperatures. Under conditions from 0 to 298.15 K, the global minimum is predicted to be a tree-like structure with one dangling singly coordinated water molecule. Above 298.15 K, higher entropy tree-like isomers with two or more singly coordinated water molecules are favored. These assignments are generally consistent with experimental IR spectra of (H3O+)(H2O)8 obtained at 150 K.

A sampling problem in molecular dynamics simulations of macromolecules.

Correlations in low-frequency atomic displacements predicted by molecular dynamics simulations on the order of 1 ns are undersampled for the time scales currently accessible by the technique. This is shown with three different representations of the fluctuations in a macromolecule: the reciprocal space of crystallography using diffuse x-ray scattering data, real three-dimensional Cartesian space using covariance matrices of the atomic displacements, and the 3N-dimensional configuration space of the protein using dimensionally reduced projections to visualize the extent to which phase space is sampled.

Molecular dynamics investigation on edge stress and shape transition in graphene nanoribbons

Graphene nanoribbon (GNR) with free edges demonstrates unique pre-existing edge energy and edge stress, leading to non-flat morphologies. Using molecular dynamics (MD) methods, we evaluated edge energies as well as edge stresses for four different edge types, including regular edges (armchair and zigzag), armchair edge terminated with hydrogen and reconstructed armchair. The results showed that compressive stress exists in the regular and hydrogen-terminated edges along the edge direction. In contrast, the reconstructed armchair edge is generally subject to tension. Furthermore, we also investigated shape transition between flat and rippled configurations of GNRs with different free edges. It was found that the pre-existing stress at free edges can greatly influence the initial energy state and the shape transition.

Molecular dynamics simulation of structural characteristics in metal cluster deposition on surfaces

The deposition of small metal clusters (Cu, Au and Al) on f.c.c. metals (Cu, Au and Ni) has been studied by molecular dynamics simulation using Finnis–Sinclair (FS) potential. The impact energy varied from 0.01 to 10 eV/atom. First, the deposition of single cluster was simulated. We observed that, even at much lower energy, a small cluster with (Ih) icosahedral symmetry was reconstructed to match the substrate structure (f.c.c.) after deposition. Next, clusters were modeled to drop, one after the other, on the surface. The nanostructure was found by soft landing of Au clusters on Cu with increasing coverage, where interfacial energy dominates. While at relatively higher deposition energy (a few eV), the ordered f.c.c.-like structure was observed in the first adlayer of the film formed by Al clusters depositing on Ni substrate. This characteristic is mainly attributive to the ballistic collision. Our results indicate that the surface morphology synthesized by cluster deposition could be controlled by experimental parameters, which will be helpful for controlled design of nanostructure.

Molecular dynamics study of ‘contact epitaxy’ in Ag clusters supported on a copper (001) surface

In this paper, the formation of heteroepitaxial interfacial layers was investigated by molecular dynamics simulation of soft silver particles landing on the (001) surface of single-crystal copper. In our simulations, the clusters Ag13, Ag55, Ag147 and Ag688 were chosen as projectiles. A small cluster will rearrange into an f.c.c. structure when it is supported on the substrate, due to the large value of its surface/volume ratio. Contact epitaxy appeared in large clusters. The characteristic structure of an epitaxial layer in large silver cluster shows the 〈111〉 direction to be the preferential orientation of heteroepitaxial layers on the surface because of the lattice mismatch between the cluster and the substrate. This was confirmed by studying soft landing events in other systems (Au/Cu and Al/Ni).