[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 (KMC) method with on-the-fly catalog building
capabilities. For mono- and di-vacancies, 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 1 to 6 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. These results show the importance of correctly
including long-range elastic effects for understanding microscopic structural
[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
[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.
Chemical Society Reviews 04/2014; · 24.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We study ion-damaged crystalline silicon by combining nanocalorimetric experiments with an off-lattice kinetic Monte Carlo simulation to identify the atomistic mechanisms responsible for the structural relaxation over long time scales. We relate the logarithmic relaxation, observed in a number of disordered systems, with heat-release measurements. The microscopic mechanism associated with this logarithmic relaxation can be described as a two-step replenish and relax process. As the system relaxes, it reaches deeper energy states with logarithmically growing barriers that need to be unlocked to replenish the heat-releasing events leading to lower-energy configurations.
[Show abstract][Hide abstract] ABSTRACT: The nature of structural relaxation in disordered systems such as amorphous silicon (a-Si) remains a fundamental issue in our attempts at understanding these materials. While a number of experiments suggest that mechanisms similar to those observed in crystals, such as vacancies, could dominate the relaxation, theoretical arguments point rather to the possibility of more diverse pathways. Using the kinetic activation-relaxation technique, an off-lattice kinetic Monte Carlo method with on-the-fly catalog construction, we resolve this question by following 1000 independent vacancies in a well-relaxed a-Si model at 300 K over a timescale of up to one second. Less than one percent of these survive over this period of time and none diffuse more than once, showing that relaxation and diffusion mechanisms in disordered systems are fundamentally different from those in the crystal.
[Show abstract][Hide abstract] ABSTRACT: Fatigue and aging of materials are, in large part, determined by the
evolution of the atomic-scale structure in response to strains and
perturbations. This coupling between microscopic structure and long time
scales remains one of the main challenges in materials study. Focusing
on a model system, ion-damaged crystalline silicon, we combine
nanocalorimetric experiments with an off-lattice kinetic Monte Carlo
simulation to identify the atomistic mechanisms responsible for the
structural relaxation over long time scales. We relate the logarithmic
relaxation, observed in a number of systems, with heat-release
measurements. The microscopic mechanism associated with logarithmic
relaxation can be described as a two-step replenish and relax process.
As the system relaxes, it reaches deeper energy states with
logarithmically growing barriers that need to be unlocked to replenish
the heat-releasing events leading to lower energy configurations.
[Show abstract][Hide abstract] ABSTRACT: The contribution of vacancy-like defects to the relaxation of amorphous
silicon (a-Si) has been a matter of debate for a long time. Due to their
disordered nature, there is a large number local environments in which
such a defect can exists. Previous numerical studies the vacancy in a-Si
have been limited to small systems and very short timescales. Here we
use kinectic ART (k-ART), an off-lattice kinetic Monte-Carlo simulation
method with on-the-fly catalog building [1,2] to study the time
evolution of 1000 different single vacancy configurations in a
well-relaxed a-Si model. Our results show that most of the vacancies are
annihlated quickly. In fact, while 16% of the 1000 isolated vacancies
survive for more than 1 ns of simulated time, 0.043% remain after 1 ms
and only 6 of them survive longer than 0.1 second. Diffusion of the full
vacancy is only seen in 19% of the configurations and diffusion usually
leads directly to the annihilation of the defect. The actual
annihilation event, in which one of the defective atoms fills the
vacancy, is usually similar in all the configurations but local bonding
environment heavily influence its activation barrier and relaxation
energy. [4pt]  El-Mellouhi et al,Phys. Rev B. 78, (2008)[0pt] 
Beland et al., Phys. Rev. E. 84, (2011)
[Show abstract][Hide abstract] ABSTRACT: Because of the long-time scale involved, the activated diffusion of
point defects is often studied in standard molecular dynamics at high
temperatures only, making it more difficult to characterize complex
diffusion mechanisms. Here, we turn to the study of point defect
diffusion in crystalline silicon using kinetic ART (kART)[1-2], an
off-lattice kinetic Monte Carlo method with on-the-fly catalog building
based on the activation-relaxation technique (ART nouveau). By
generating catalogs of diffusion mechanisms and fully incorporating
elastic and off-lattice effects, kART is a unique tool for
characterizing this problem. More precisely, using kART with the
standard Stillinger-Weber potential we consider the evolution of
crystalline cells with 1 to 4 vacancies and 1 to 4 interstitials at
various temperatures and to provide a detailed picture of both the
atomistic diffusion mechanisms and overall kinetics in addition to
identifying special configurations such as a 2-interstitial
super-diffuser. [4pt]  F. El-Mellouhi, N. Mousseau and L.J. Lewis,
Phys. Rev. B. 78, 153202 (2008)[0pt]  L. K. Béland, P.
Brommer, F. El-Mellouhi, J.-F. Joly and N. Mousseau, Phys. Rev. E 84,
[Show abstract][Hide abstract] ABSTRACT: In the last two decades, there has been a considerable interest in the
development of accelerated numerical methods for sampling the energy
landscape of complex materials. Many of these methods are based on the
kinetic Monte Carlo (KMC) algorithm introduced 40 years ago. This is the
case of kinetic ART, for example, which uses a very efficient
transition-state searching method, ART nouveau, coupled with a
topological tool, NAUTY, to offer an off-lattice KMC method with
on-the-fly catalog building to study complex systems, such as
ion-bombarded and amorphous materials, on timescales of a second or
more. Looking at two systems, vacancy aggregation in Fe and energy
relaxation in ion-bombarded c-Si, we characterize the changes in the
energy landscape and the relation to its time evolution with kinetic ART
and its correspondence with the well-known Bell-Evans-Polanyi principle
used in chemistry.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease is the most common form of senile dementia, affecting more than 24 million people worldwide. It is characterised pathologically by abnormally high levels of neurofibrillary tangles resulting from the accumulation of tau protein in dead and dying neurons, and by elevated numbers of senile plaques in the cortex and hippocampus of the brain. The major component of senile plaques is a small protein of 39–43 amino acids called amyloid-β (Aβ). Thus far, no treatment has been shown to slow the progression of sporadic and familial Alzheimer's disease.
A large body of evidence points, however, to the early Aβ-formed oligomers as the primary toxic species in Alzheimer's disease. A powerful strategy for developing pharmaceutical treatments against Alzheimer's is to elucidate the pathways of oligomer formation and determine the structures of the toxic aggregates.
This book provides a panoramic view across recent in vitro and in vivo studies along with state-of-the-art computer simulations, designed to increase the readers' understanding of Aβ oligomerisation and fibril formation. At the same time, the book delves into the pathogenesis of familial and sporadic Alzheimer's disease at the atomic level of detail.
Written by leading authors in their respective fields, this book will be valuable to all scientists working on Alzheimer's disease.
[Show abstract][Hide abstract] ABSTRACT: The small amyloid-forming GNNQQNY fragment of the prion sequence has been the subject of extensive experimental and numerical studies over the last few years. Using unbiased molecular dynamics with the OPEP coarse-grained potential, we focus here on the onset of aggregation in a 20-mer system. With a total of 16.9 [Formula: see text] of simulations at 280 K and 300 K, we show that the GNNQQNY aggregation follows the classical nucleation theory (CNT) in that the number of monomers in the aggregate is a very reliable descriptor of aggregation. We find that the critical nucleus size in this finite-size system is between 4 and 5 monomers at 280 K and 5 and 6 at 300 K, in overall agreement with experiment. The kinetics of growth cannot be fully accounted for by the CNT, however. For example, we observe considerable rearrangements after the nucleus is formed, as the system attempts to optimize its organization. We also clearly identify two large families of structures that are selected at the onset of aggregation demonstrating the presence of well-defined polymorphism, a signature of amyloid growth, already in the 20-mer aggregate.
[Show abstract][Hide abstract] ABSTRACT: Magnetism in two dimensional atomic sheets has attracted considerable interest as its existence could allow the development of electronic and spintronic devices. The existence of magnetism is not sufficient for devices, however, as states must be addressable and modifiable through the application of an external drive. We show that defects in hexagonal boron nitride present a strong interplay between the N-N distance in the edge and the magnetic moments of the defects. By stress-induced geometry modifications, we change the ground state magnetic moment of the defects. This control is made possible by the triangular shape of the defects as well as the strong spin localisation in the magnetic state.
[Show abstract][Hide abstract] ABSTRACT: Several neurodegenerative diseases are associated with the polyglutamine (polyQ) repeat disorder in which a segment of consecutive glutamines in the native protein is produced with too many glutamines. Huntington's disease, for example, is related to the misfolding of the Huntingtin protein which occurs when the polyQ segment has more than approximately 36 glutamines. Experimentally, it is known that the polyQ segment alone aggregates into β-rich conformations such as amyloid fibrils. Its aggregation is modulated by the number of glutamine residues as well as by the surrounding amino acid sequences such as the 17-amino-acid N-terminal fragment of Huntingtin which increases the aggregation rate. Little structural information is available, however, regarding the first steps of aggregation and the atomistic mechanisms of oligomerization are yet to be described. Following previous coarse-grained replica-exchange molecular dynamics simulations that show the spontaneous formation of a nanotube consisting of two intertwined antiparallel strands (Laghaei, R.; Mousseau, N. J. Chem. Phys.2010, 132, 165102), we study this configuration and some extensions of it using all-atom explicit solvent MD simulations. We compare two different lengths for the polyQ segment, 40 and 30 glutamines, and we investigate the impact of the Huntingtin N-terminal residues (htt(NT)). Our results show that the dimeric nanotubes can provide a building block for the formation of longer nanotubes (hexamers and octamers). These longer nanotubes are characterized by large β-sheet propensities and a small solvent exposure of the main-chain atoms. Moreover, the oligomerization between two nanotubes occurs through the formation of protein/protein H-bonds and can result in an elongation of the water-filled core. Our results also show that the htt(NT) enhances the structural stability of the β-rich seeds, suggesting a new mechanism by which it can increase the aggregation rate of the amyloidogenic polyQ sequence.
The Journal of Physical Chemistry B 09/2012; 116(40):12168-79. · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using the art nouveau method, we study the initial stages of silicon oxide formation. After validating the method's parameters with the characterization of point defects diffusion mechanisms in pure Stillinger-Weber silicon, which allows us to recover some known results and to detail vacancy and self-interstitial diffusion paths, the method is applied onto a system composed of an oxygen layer deposited on a silicon substrate. We observe the oxygen atoms as they move rapidly into the substrate. From these art nouveau simulations, we extract the energy barriers of elementary mechanisms involving oxygen atoms and leading to the formation of an amorphouslike silicon oxide. We show that the kinetics of formation can be understood in terms of the energy barriers between various coordination environments.
[Show abstract][Hide abstract] ABSTRACT: We present an adaptation of the ART-nouveau energy surface sampling method to the problem of loop structure prediction. This method, previously used to study protein folding pathways and peptide aggregation, is well suited to the problem of sampling the conformation space of large loops by targeting probable folding pathways instead of sampling exhaustively that space. The number of sampled conformations needed by ART nouveau to find the global energy minimum for a loop was found to scale linearly with the sequence length of the loop for loops between 8 and about 20 amino acids. Considering the linear scaling dependence of the computation cost on the loop sequence length for sampling new conformations, we estimate the total computational cost of sampling larger loops to scale quadratically compared to the exponential scaling of exhaustive search methods.
Proteins Structure Function and Bioinformatics 04/2012; 80(7):1883-94. · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The ATP binding cassette (ABC) transporter family of proteins contains members involved in ATP-mediated import or export of ligands at the cell membrane. For the case of exporters, the translocation mechanism involves a large-scale conformational change that involves a clothespin-like motion from an inward-facing open state, able to bind ligands and adenosine triphosphate (ATP), to an outward-facing closed state. Our work focuses on SAV1866, a bacterial member of the ABC transporter family for which the structure is known for the closed state. To evaluate the ability of this protein to undergo conformational changes at physiological temperature, we first performed conventional molecular dynamics (MD) on the cocrystallized adenosine diphosphate (ADP)-bound structure and on a nucleotide-free structure. With this assessment of SAV1866's stability, conformational changes were induced by steered molecular dynamics (SMD), in which the nucleotide binding domains (NBD) were pushed apart, simulating the ATP hydrolysis energy expenditure. We found that the transmembrane domain is not easily perturbed by large-scale motions of the NBDs.
The Journal of Physical Chemistry B 03/2012; 116(9):2934-42. · 3.61 Impact Factor