[Show abstract][Hide abstract]ABSTRACT: Adsorption and dissociation of hydrocarbons on metallic surfaces represent crucial steps to carburization of metal. Here, we use density functional theory total energy calculations with the climbing-image nudged elastic band method to estimate the adsorption energies and dissociation barriers for different CO coverages with surface supercells of different sizes. For the absorption of CO, the contribution from van der Waals interaction in the computation of adsorption parameters is found important in small systems with high CO-coverages. The dissociation process involves carbon insertion into the Fe surface causing a lattice deformation that requires a larger surface system for unrestricted relaxation. We show that, in larger surface systems associated with dilute CO-coverages, the dissociation barrier is significantly decreased. The elastic deformation of the surface is generic and can potentially applicable for all similar metal-hydrocarbon reactions and therefore a dilute coverage is necessary for the simulation of these reactions as isolated processes.
[Show abstract][Hide abstract]ABSTRACT: The first exon of Huntingtin-a protein with multiple biological functions whose misfolding is related to Huntington's disease-modulates its localization, aggregation, and function within the cell. It is composed of a 17-amino-acid amphipathic segment (Htt17), an amyloidogenic segment of consecutive glutamines (QN), and a proline-rich segment. Htt17 is of fundamental importance: it serves as a membrane anchor to control the localization of huntingtin, it modulates huntingtin's function through posttranslational modifications, and it controls the self-assembly of the amyloidogenic QN segment into oligomers and fibrils. Experimentally, the conformational ensemble of the Htt17 monomer, as well as the impact of the polyglutamine and proline-rich segments, remains, however, mostly uncharacterized at the atomic level due to its intrinsic flexibility. Here, we unveil the free-energy landscape of Htt17, Htt17Q17, and Htt17Q17P11 using Hamiltonian replica exchange combined with well-tempered metadynamics. We characterize the free-energy landscape of these three fragments in terms of a few selected collective variables. Extensive simulations reveal that the free energy of Htt17 is dominated by a broad ensemble of configurations that agree with solution NMR chemical shifts. Addition of Q17 at its carboxy-terminus reduces the extent of the main basin to more extended configurations of Htt17 with lower helix propensity. Also, the aliphatic carbons of Q17 partially sequester the nonpolar amino acids of Htt17. For its part, addition of Q17P11 shifts the overall landscape to a more extended and helical Htt17 stabilized by interactions with Q17 and P11, which almost exclusively form a PPII-helix, as well as by intramolecular H-bonds and salt bridges. Our characterization of Huntingtin's amino-terminus provides insights into the structural origin of its ability to oligomerize and interact with phospholipid bilayers, processes closely linked to the biological functions of this protein.
[Show abstract][Hide abstract]ABSTRACT: Diffusion of carbon in iron is associated with processes such as carburization and the production of steels. In this work, the kinetic activation-relaxation technique (k-ART) - an off-lattice self-learning kinetic Monte Carlo (KMC) algorithm - is used to study this phenomenon over long time scales. Coupling the open-ended ART nouveau technique to generate on-the-fly activated events and NAUTY, a topological classification for cataloging, k-ART reaches timescales that range from microseconds to seconds while fully taking into account long-range elastic effects and complex events, characterizing in details the energy landscape in a way that cannot be done with standard molecular dynamics (MD) or KMC. The diffusion mechanisms and pathways for one to four carbon interstitials, and a single vacancy coupled with one to several carbons are studied. In bulk Fe, k-ART predicts correctly the 0.815 eV barrier for a single C-interstitial as well as the stressed induced energy-barrier distribution around this value for 2 and 4 C interstitials. For vacancy-carbon complex, simulations recover the DFT-predicted ground state. K-ART also identifies a trapping mechanism for the vacancy through the formation of a dynamical complex, involving C and neighboring Fe atoms, characterized by hops over barriers ranging from ∼0.41 to ∼0.72 eV that correspond, at room temperature, to trapping time of hours. At high temperatures, this complex can be broken by crossing a 1.5 eV barrier, leading to a state ∼0.8 eV higher than the ground state, allowing diffusion of the vacancy. A less stable complex is formed when a second C is added, characterized by a large number of bound excited states that occupy two cells. It can be broken into a V-C complex and a single free C through a 1.11 eV barrier.
[Show abstract][Hide abstract]ABSTRACT: Many neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, are characterized by the presence of amyloid fibers. Recently, attention has turned from the fibers to the early stages of oligomerization where toxicity could be highest. Here, we focus on the interactions between non-Aβ amyloid component of a-synuclein (NAC) and Aβ 1-40, two proteins found in amyloid fibrils associated with Alzheimer's disease. We combine the coarse-grained OPEP potential with a Hamiltonian and temperature replica exchange molecular dynamics simulation (HT-REMD) to identify mechanisms leading to the formation of secondary structures promoting fibrillation. We observe that the propensity to form beta-sheet remains the same for Aβ 1-40 whereas is decreases significantly for NAC. In particular, the 25-35 region of Aβ 1-40 is a significant area of secondary structure stabilization with NAC. The ionic interactions between salt-bridge D23 and K28 in Aβ 1-40 and K20 and E23 in NAC of the heterogeneous dimer are consistent with the salt-bridges found in NAC and Aβ 1-40 homogenous dimers and allow us to see that these interactions don't necessarily dominate the interchain stabilizations. Our numerical simulation also show the formation of interaction between the early oligomer of NAC and Aβ 1-40.
Article · Sep 2015 · Behaviour and Information Technology
[Show abstract][Hide abstract]ABSTRACT: We study point-defect diffusion in crystalline silicon using the kinetic activation-relaxation technique (k-ART), an off-lattice kinetic Monte Carlo method with on-the-fly catalog building capabilities based on the activation-relaxation technique (ART nouveau), coupled to the standard Stillinger-Weber potential. We focus more particularly on the evolution of crystalline cells with one to four vacancies and one to four interstitials in order to provide a detailed picture of both the atomistic diffusion mechanisms and overall kinetics. We show formation energies, activation barriers for the ground state of all eight systems, and migration barriers for those systems that diffuse. Additionally, we characterize diffusion paths and special configurations such as dumbbell complex, di-interstitial (IV-pair+2I) superdiffuser, tetrahedral vacancy complex, and more. This study points to an unsuspected dynamical richness even for this apparently simple system that can only be uncovered by exhaustive and systematic approaches such as the kinetic activation-relaxation technique.
[Show abstract][Hide abstract]ABSTRACT: We present a new semiempirical potential for graphene, which includes also an out-of-plane energy term. This novel potential is developed from density functional theory (DFT) calculations for small numbers of atoms
and can be used for configurations with millions of atoms. Our simulations show that buckling caused by typical defects such as the Stone−Wales (SW) defect extends to hundreds of nanometers. Surprisingly, this long-range
relaxation lowers the defect formation energy dramaticallyby a factor of 2 or 3implying that previously published DFT-calculated defect formation energies suffer from large systematic errors. We also show the applicability of the novel potential to other long-range defects including line dislocations and grain boundaries, all of which exhibit pronounced out-of-plane relaxations. We show that the energy as a function of dislocation separation diverges logarithmically for flat graphene but converges to a constant for freestanding buckled graphene. A potential in which the atoms are attracted to the 2D plane restores the logarithmic behavior of the
energy. Future simulations employing this potential will elucidate the influence of the typical long-range buckling and rippling on the physical properties of graphene.
Full-text Article · Apr 2015 · The Journal of Physical Chemistry C
[Show abstract][Hide abstract]ABSTRACT: The properties of materials, even at the atomic level, evolve on macroscopic time scales. Following this evolution through simulation has been a challenge for many years. For lattice-based activated diffusion, kinetic Monte Carlo has turned out to be an almost perfect solution. Various accelerated molecular dynamical schemes, for their part, have allowed the study on long time scale of relatively simple systems. There is still a need, however, for methods able to handle complex materials such as alloys and disordered systems. Here, we review the kinetic Activation–Relaxation Technique (k-ART), one of a handful of off-lattice kinetic Monte Carlo methods, with on-the-fly cataloging, that have been proposed in the last few years.
[Show abstract][Hide abstract]ABSTRACT: Researchers present an in-depth review on the contribution of biophysical and biochemical studies and computer simulations to characterize the molecular structures of Aβ1-40/1-42 monomers, oligomers, protofibrils, and amyloid fibrils in aqueous solution. They focus their current knowledge of the Aβ1-40/1-42 nucleus and the structures and dynamics of Aβ1-40/1-42 oligomers in proximity of or at the membrane. They also the available information regarding the interactions of Aβ monomers and oligomers with ion metals, cellular partners, and potential inhibitors.
[Show abstract][Hide abstract]ABSTRACT: Islet amyloid polypeptide, IAPP or amylin, is a 37-residue peptide hormone coexpressed with insulin by pancreatic β-cells. The aggregation of human IAPP (hIAPP) into amyloid deposits is associated with type II diabetes. Substantial evidence suggests that the interaction of anionic membranes with hIAPP may facilitate peptide aggregation and the N-terminal 1~19 fragment (IAPP1-19) plays an important role in peptide-membrane interaction. As a first step to understand how structural differences between human and rat IAPP peptides in membrane may influence the later oligomerization process, we have investigated the structures and orientations of hIAPP1-19 and the less toxic rIAPP1-19 (i.e. the H18R mutant of hIAPP1-19) monomers in anionic POPG bilayers by performing replica exchange molecular dynamics (REMD) simulations. On the basis of ~20-μs REMD simulations started from a random coil conformation of the peptide placed in water, we find that unfolded h(r)IAPP1-19 can insert into the bilayers and the membrane-bound peptide stays mainly at the lipid head-tail interface. hIAPP1-19 displays higher propensity to adopt helical conformations than rIAPP1-19, especially in the L12~L16 region. The helical conformation is oriented parallel to the bilayer surface and buried in the membrane 0.3~0.8 nm below the phosphorus atoms, consistent with previous electron paramagnetic resonance data. The helical conformation is an amphiphilic helix with its hydrophilic and hydrophobic faces pointing respectively to the lipid head and tail regions. The H18R substitution enhances the electrostatic interactions of IAPP1-19 with membrane, while weakens the intra-peptide interactions crucial for helix formation, thus leading to lower helix propensity of rIAPP1-19. Implications of our simulation results on the membrane-mediated IAPP1-19 oligomerization are discussed.
Full-text Article · Feb 2015 · The Journal of Physical Chemistry B
[Show abstract][Hide abstract]ABSTRACT: We propose NaFeZr2F11 and NaFeTi2F11 as novel materials for Na intercalation cathodes. The average sodium intercalation voltage for these compounds is about 4.0 V from first principles computations. The origin of this large voltage for a nominal Fe2 +/Fe3 + redox couple is proposed to be a combination of the fluorine “booster” effect, the inductive effect and the stiffness of the proposed structure upon desodiation.
Article · Dec 2014 · Electrochemistry Communications
[Show abstract][Hide abstract]ABSTRACT: Vacancy diffusion and clustering processes in body-centered-cubic (bcc) Fe are studied using the kinetic activation-relaxation technique (k-ART), an off-lattice kinetic Monte Carlo method with on-the-fly catalog building capabilities. For monovacancies and divacancies, k-ART recovers previously published results while clustering in a 50-vacancy simulation box agrees with experimental estimates. Applying k-ART to the study of clustering pathways for systems containing from one to six vacancies, we find a rich set of diffusion mechanisms. In particular, we show that the path followed to reach a hexavacancy cluster influences greatly the associated mean-square displacement. Aggregation in a 50-vacancy box also shows a notable dispersion in relaxation time associated with effective barriers varying from 0.84 to 1.1 eV depending on the exact pathway selected. We isolate the effects of long-range elastic interactions between defects by comparing to simulations where those effects are deliberately suppressed. This allows us to demonstrate that in bcc Fe, suppressing long-range interactions mainly influences kinetics in the first 0.3 ms, slowing down quick energy release cascades seen more frequently in full simulations, whereas long-term behavior and final state are not significantly affected.
[Show abstract][Hide abstract]ABSTRACT: In recent years, much effort has focused on the early stages of aggregation and the formation of amyloid oligomers. Aggregation processes for these proteins are complex and their non-equilibrium nature makes any experimental study very difficult. Under these conditions, simulations provide a useful alternative for understanding the dynamics of the early stages of oligomerization. Here, we focus on the non-Aβ amyloid component (NAC) of the monomer, dimer, and trimer of α-synuclein, an important 35-residue sequence involved in the aggregation and fibrillation of this protein associated with Parkinson's disease. Using Hamiltonian and temperature replica exchange molecular dynamics simulations combined with the coarse grained Optimized Potential for Efficient peptide structure Prediction potential, we identify the role of the various regions and the secondary structures for the onset of oligomerization. For this sequence, we clearly observe the passage from α-helix to β-sheet, a characteristic transition of amyloid proteins. More precisely, we find that the NAC monomer is highly structured with two α-helical regions, between residues 2-13 and 19-25. As the dimer and trimer form, β-sheet structures between residues 2-14 and 26-34 appear and rapidly structure the system. The resulting conformations are much more structured than similar dimers and trimers of β-amyloid and amylin proteins and yet display a strong polymorphism at these early stages of aggregation. In addition to its inherent experimental interest, comparison with other sequences shows that NAC could be a very useful numerical model for understanding the onset of aggregation.
Full-text Article · Oct 2014 · The Journal of Chemical Physics
[Show abstract][Hide abstract]ABSTRACT: The efficiency of minimum-energy configuration searching algorithms is
closely linked to the energy landscape structure of complex systems. Here we
characterize this structure by following the time evolution of two systems,
vacancy aggregation in Fe and energy relaxation in ion-bombarded c-Si, using
the kinetic Activation-Relaxation Technique (k-ART), an off-lattice kinetic
Monte Carlo (KMC) method, and the well-known Bell-Evans-Polanyi (BEP)
principle. We also compare the efficiency of two methods for handling
non-diffusive flickering states -- an exact solution and a Tabu-like approach
that blocks already visited states. Comparing these various simulations allow
us to confirm that the BEP principle does not hold for complex system since
forward and reverse energy barriers are completely uncorrelated. This means
that following the lowest available energy barrier, even after removing the
flickering states, leads to rapid trapping: relaxing complex systems requires
crossing high-energy barriers in order to access new energy basins, in
agreement with the recently proposed replenish-and-relax model [B\'eland et
al., PRL 111, 105502 (2013)] This can be done by forcing the system through
these barriers with Tabu-like methods. Interestingly, we find that following
the fundamental kinetics of a system, though standard KMC approach, is at least
as efficient as these brute-force methods while providing the correct kinetics
Full-text Article · Jul 2014 · Journal of Chemical Theory and Computation
[Show abstract][Hide abstract]ABSTRACT: We investigate Ge mixing at the Si(001) surface and characterize the $2\times
N$ Si(001) reconstruction by means of hybrid quantum and molecular mechanics
calculations (QM/MM). Avoiding fake elastic dampening, this scheme allows to
correctly take into account long range deformation induced by reconstruted and
defective surfaces. We focus in particular on the dimer vacancy line (DVL) and
its interaction with Ge adatoms. We first show that calculated formation
energies for these defects are highly dependent on the choice of chemical
potential and that the latter must be chosen carefully. Characterizing the
effect of the DVL on the deformation field, we also find that the DVL favors Ge
segregation in the fourth layer close to the DVL. Using the
activation-relaxation technique (ART nouveau) and QM/MM, we show that a complex
diffusion path permits the substitution of the Ge atom in the fourth layer,
with barriers compatible with mixing observed at intermediate temperature.
[Show abstract][Hide abstract]ABSTRACT: 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.
Full-text Article · Apr 2014 · Chemical Society Reviews