scholarly journals Deep learning the slow modes for rare events sampling

2021 ◽  
Vol 118 (44) ◽  
pp. e2113533118
Author(s):  
Luigi Bonati ◽  
GiovanniMaria Piccini ◽  
Michele Parrinello
Keyword(s):  
Sampling Method ◽  
Rare Events ◽  
Conformational Transition ◽  
Transfer Operator ◽  
Atomistic Simulations ◽  
Enhanced Sampling ◽  
Collective Variables ◽  
Long Time ◽  
Computational Resources

The development of enhanced sampling methods has greatly extended the scope of atomistic simulations, allowing long-time phenomena to be studied with accessible computational resources. Many such methods rely on the identification of an appropriate set of collective variables. These are meant to describe the system’s modes that most slowly approach equilibrium under the action of the sampling algorithm. Once identified, the equilibration of these modes is accelerated by the enhanced sampling method of choice. An attractive way of determining the collective variables is to relate them to the eigenfunctions and eigenvalues of the transfer operator. Unfortunately, this requires knowing the long-term dynamics of the system beforehand, which is generally not available. However, we have recently shown that it is indeed possible to determine efficient collective variables starting from biased simulations. In this paper, we bring the power of machine learning and the efficiency of the recently developed on the fly probability-enhanced sampling method to bear on this approach. The result is a powerful and robust algorithm that, given an initial enhanced sampling simulation performed with trial collective variables or generalized ensembles, extracts transfer operator eigenfunctions using a neural network ansatz and then accelerates them to promote sampling of rare events. To illustrate the generality of this approach, we apply it to several systems, ranging from the conformational transition of a small molecule to the folding of a miniprotein and the study of materials crystallization.

scholarly journals Neural networks-based variationally enhanced sampling

2019 ◽  
Vol 116 (36) ◽  
pp. 17641-17647 ◽  
Author(s):  
Luigi Bonati ◽  
Yue-Yu Zhang ◽  
Michele Parrinello
Keyword(s):  
Neural Networks ◽  
Free Energy ◽  
Atomistic Simulation ◽  
Sampling Method ◽  
Machine Learning Techniques ◽  
Enhanced Sampling ◽  
Collective Variables ◽  
Learning Techniques ◽  
Minimization Technique ◽  
Energy Surfaces

Sampling complex free-energy surfaces is one of the main challenges of modern atomistic simulation methods. The presence of kinetic bottlenecks in such surfaces often renders a direct approach useless. A popular strategy is to identify a small number of key collective variables and to introduce a bias potential that is able to favor their fluctuations in order to accelerate sampling. Here, we propose to use machine-learning techniques in conjunction with the recent variationally enhanced sampling method [O. Valsson, M. Parrinello, Phys. Rev. Lett. 113, 090601 (2014)] in order to determine such potential. This is achieved by expressing the bias as a neural network. The parameters are determined in a variational learning scheme aimed at minimizing an appropriate functional. This required the development of a more efficient minimization technique. The expressivity of neural networks allows representing rapidly varying free-energy surfaces, removes boundary effects artifacts, and allows several collective variables to be handled.

scholarly journals Enhanced Sampling of Protein Conformational Transitions via Dynamically Optimized Collective Variables

2018 ◽  
Author(s):  
Z. Faidon Brotzakis ◽  
Michele Parrinello
Keyword(s):  
Degrees Of Freedom ◽  
Conformational Transition ◽  
Conformational Dynamics ◽  
Computational Cost ◽  
Md Simulations ◽  
Conformational Transitions ◽  
Enhanced Sampling ◽  
Collective Variables ◽  
Simulation Based ◽  
Combined Data

AbstractProtein conformational transitions often involve many slow degrees of freedom. Their knowledge would give distinctive advantages since it provides chemical and mechanistic insight and accelerates the convergence of enhanced sampling techniques that rely on collective variables. In this study, we implemented a recently developed variational approach to conformational dynamics metadynamics to the conformational transition of the moderate size protein, L99A T4 Lysozyme. In order to find the slow modes of the system we combined data coming from NMR experiments as well as short MD simulations. A Metadynamics simulation based on these information reveals the presence of two intermediate states, at an affordable computational cost.

scholarly journals Coarse graining from variationally enhanced sampling applied to the Ginzburg–Landau model

2017 ◽  
Vol 114 (13) ◽  
pp. 3370-3374 ◽  
Author(s):  
Michele Invernizzi ◽  
Omar Valsson ◽  
Michele Parrinello
Keyword(s):  
Critical Point ◽  
Sampling Method ◽  
Coarse Graining ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Enhanced Sampling ◽  
Ginzburg Landau ◽  
Coarse Grained Model ◽  
Unique Approach ◽  
Physical Features

A powerful way to deal with a complex system is to build a coarse-grained model capable of catching its main physical features, while being computationally affordable. Inevitably, such coarse-grained models introduce a set of phenomenological parameters, which are often not easily deducible from the underlying atomistic system. We present a unique approach to the calculation of these parameters, based on the recently introduced variationally enhanced sampling method. It allows us to obtain the parameters from atomistic simulations, providing thus a direct connection between the microscopic and the mesoscopic scale. The coarse-grained model we consider is that of Ginzburg–Landau, valid around a second-order critical point. In particular, we use it to describe a Lennard–Jones fluid in the region close to the liquid–vapor critical point. The procedure is general and can be adapted to other coarse-grained models.

scholarly journals Microscopic description of acid–base equilibrium

2019 ◽  
Vol 116 (10) ◽  
pp. 4054-4057 ◽  
Author(s):  
Emanuele Grifoni ◽  
GiovanniMaria Piccini ◽  
Michele Parrinello
Keyword(s):  
Md Simulation ◽  
Ab Initio Molecular Dynamics ◽  
Atomistic Simulations ◽  
Limited Information ◽  
Enhanced Sampling ◽  
Acid Base ◽  
Collective Variables ◽  
Molecular Behavior ◽  
Acid Base Equilibrium ◽  
Insight Into

Acid–base reactions are ubiquitous in nature. Understanding their mechanisms is crucial in many fields, from biochemistry to industrial catalysis. Unfortunately, experiments give only limited information without much insight into the molecular behavior. Atomistic simulations could complement experiments and shed precious light on microscopic mechanisms. The large free-energy barriers connected to proton dissociation, however, make the use of enhanced sampling methods mandatory. Here we perform an ab initio molecular dynamics (MD) simulation and enhance sampling with the help of metadynamics. This has been made possible by the introduction of descriptors or collective variables (CVs) that are based on a conceptually different outlook on acid–base equilibria. We test successfully our approach on three different aqueous solutions of acetic acid, ammonia, and bicarbonate. These are representative of acid, basic, and amphoteric behavior.

Practical electron tomography

1995 ◽  
Vol 53 ◽  
pp. 742-743
Author(s):  
C.L. Woodcock
Keyword(s):  
Electron Tomography ◽  
Tomographic Reconstruction ◽  
Three Dimensional ◽  
3D Shape ◽  
Computational Resources ◽  
Shape Of Particles

Despite the potential of the technique, electron tomography has yet to be widely used by biologists. This is in part related to the rather daunting list of equipment and expertise that are required. Thanks to continuing advances in theory and instrumentation, tomography is now more feasible for the non-specialist. One barrier that has essentially disappeared is the expense of computational resources. In view of this progress, it is time to give more attention to practical issues that need to be considered when embarking on a tomographic project. The following recommendations and comments are derived from experience gained during two long-term collaborative projects.Tomographic reconstruction results in a three dimensional description of an individual EM specimen, most commonly a section, and is therefore applicable to problems in which ultrastructural details within the thickness of the specimen are obscured in single micrographs. Information that can be recovered using tomography includes the 3D shape of particles, and the arrangement and dispostion of overlapping fibrous and membranous structures.

Enhancing the power generation of Rhodopseudomonas palustris-based MFC

2020 ◽  
Vol 64 (1-4) ◽  
pp. 1261-1268
Author(s):  
Shu Otani ◽  
Dang-Trang Nguyen ◽  
Kozo Taguchi
Keyword(s):  
Activated Carbon ◽  
Rhodopseudomonas Palustris ◽  
Ozone Treatment ◽  
Maximum Power Density ◽  
On Demand ◽  
Long Time ◽  
Dry Conditions ◽  
Carbon Sheet ◽  
Uv Ozone

In this study, a portable and disposable paper-based microbial fuel cell (MFC) was fabricated. The MFC was powered by Rhodopseudomonas palustris bacteria (R. palustris). An activated carbon sheet-based anode pre-loaded organic matter (starch) and R. palustris was used. By using starch in the anode, R. palustris-loaded on the anode could be preserved for a long time in dry conditions. The MFC could generate electricity on-demand activated by adding water to the anode. The activated carbon sheet anode was treated by UV-ozone treatment to remove impurities and to improve its hydrophilicity before being loaded with R. palustris. The developed MFC could generate the maximum power density of 0.9 μW/cm2 and could be preserved for long-term usage with little performance degradation (10% after four weeks).

Charlemagne’s Health in ‘Old Age’: Did It Affect Carolingian Military Strategy?

Mediaevistik ◽  
2020 ◽  
Vol 32 (1) ◽  
pp. 11-53
Author(s):  
Bernard S. Bachrach
Keyword(s):  
Old Age ◽  
The Political ◽  
Military Strategy ◽  
The West ◽  
Long Time

During the first thirty-three years of his reign as king of the Franks, i.e., prior to his coronation as emperor on Christmas day 800, Charlemagne, scholars generally agree, pursued a successful long-term offensive and expansionist strategy. This strategy was aimed at conquering large swaths of erstwhile imperial territory in the west and bringing under Carolingian rule a wide variety of peoples, who either themselves or their regional predecessors previously had not been subject to Frankish regnum.1 For a very long time, scholars took the position that Charlemagne continued to pursue this expansionist strategy throughout the imperial years, i.e., from his coronation on Christmas Day 800 until his final illness in later January 814. For example, Louis Halphen observed: “comme empereur, Charles poursuit, sans plus, l’oeuvre entamée avant l’an 800.”2 F. L. Ganshof, who also wrote several studies treating Charlemagne’s army, was in lock step with Halphen and observed: “As emperor, Charlemagne pursued the political and military course he had been following before 25 December 800.”3

The Spread of Pollutants from Harbour Sludge Depots

1984 ◽  
Vol 16 (3-4) ◽  
pp. 623-633
Author(s):  
M Loxham ◽  
F Weststrate
Keyword(s):  
Time Scales ◽  
Molecular Diffusion ◽  
Near Field ◽  
Parameter Analysis ◽  
Migration Patterns ◽  
Long Time ◽  
Dilution Effects ◽  
Short Time ◽  
Harbour Sludge

It is generally agreed that both the landfill option, or the civil techniques option for the final disposal of contaminated harbour sludge involves the isolation of the sludge from the environment. For short time scales, engineered barriers such as a bentonite screen, plastic sheets, pumping strategies etc. can be used. However for long time scales the effectiveness of such measures cannot be counted upon. It is thus necessary to be able to predict the long term environmenttal spread of contaminants from a mature landfill. A model is presented that considers diffusion and adsorption in the landfill site and convection and adsorption in the underlaying aquifer. From a parameter analysis starting form practical values it is shown that the adsorption behaviour and the molecular diffusion coefficient of the sludge, are the key parameters involved in the near field. The dilution effects of the far field migration patterns are also illustrated.

The Many Faces of Socioeconomic Change

2017 ◽  
Author(s):  
John Toye
Keyword(s):  
Socioeconomic Development ◽  
Adam Smith ◽  
First Century ◽  
Social Progress ◽  
Long Time ◽  
The Face ◽  
Scientific Expertise ◽  
The Many ◽  
Century Development

This book provides a survey of different ways in which economic sociocultural and political aspects of human progress have been studied since the time of Adam Smith. Inevitably, over such a long time span, it has been necessary to concentrate on highlighting the most significant contributions, rather than attempting an exhaustive treatment. The aim has been to bring into focus an outline of the main long-term changes in the way that socioeconomic development has been envisaged. The argument presented is that the idea of socioeconomic development emerged with the creation of grand evolutionary sequences of social progress that were the products of Enlightenment and mid-Victorian thinkers. By the middle of the twentieth century, when interest in the accelerating development gave the topic a new impetus, its scope narrowed to a set of economically based strategies. After 1960, however, faith in such strategies began to wane, in the face of indifferent results and general faltering of confidence in economists’ boasts of scientific expertise. In the twenty-first century, development research is being pursued using a research method that generates disconnected results. As a result, it seems unlikely that any grand narrative will be created in the future and that neo-liberalism will be the last of this particular kind of socioeconomic theory.

scholarly journals Acceptance of a Symptom-Based Approach for COVID-19 rtRT-PCR Testing to Conserve Resources in a Lower Middle-Income Setting

2021 ◽  
Vol 12 ◽  
pp. 215013272098771
Author(s):  
S. M. Rashed Ul Islam ◽  
Tahmina Akther ◽  
Md. Abdullah Omar Nasif ◽  
Sharmin Sultana ◽  
Saif Ullah Munshi
Keyword(s):  
Primary Method ◽  
Chain Reaction ◽  
Middle Income ◽  
Clinical Recovery ◽  
Clinical Presentations ◽  
Long Time ◽  
Nasopharyngeal Secretion ◽  
Polymerase Chain ◽  
Set Up

SARS-CoV-2 initially emerged in Wuhan, China in late 2019. It has since been recognized as a pandemic and has led to great social and economic disruption globally. The Reverse Transcriptase Real-Time Polymerase Chain Reaction (rtRT-PCR) has become the primary method for COVID-19 testing worldwide. The method requires a specialized laboratory set up. Long-term persistence of SARS-CoV-2 RNA in nasopharyngeal secretion after full clinical recovery of the patient is regularly observed nowadays. This forces the patients to spend a longer period in isolation and test repeatedly to obtain evidence of viral clearance. Repeated COVID-19 testing in asymptomatic or mildly symptomatic cases often leads to extra workload for laboratories that are already struggling with a high specimen turnover. Here, we present 5 purposively selected cases with different patterns of clinical presentations in which nasopharyngeal shedding of SARS-CoV-2 RNA was observed in patients for a long time. From these case studies, we emphasized the adoption of a symptom-based approach for discontinuing transmission-based precautions over a test-based strategy to reduce the time spent by asymptomatic and mildly symptomatic COVID-19 patients in isolation. A symptom-based approach will also help reduce laboratory burden for COVID-19 testing as well as conserve valuable resources and supplies utilized for rtRT-PCR testing in an emerging lower-middle-income setting. Most importantly, it will also make room for critically ill COVID-19 patients to visit or avail COVID-19 testing at their convenience.

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