The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Michele Parrinello - One of the best experts on this subject based on the ideXlab platform.

  • Metadynamics of paths
    Physical Review Letters, 2020
    Co-Authors: Davide Mandelli, Michele Parrinello, Barak Hirshberg
    Abstract:

    We present a method to sample reactive pathways via biased molecular dynamics simulations in trajectory space. We show that the use of enhanced sampling techniques enables unconstrained exploration of multiple reaction routes. Time correlation functions are conveniently computed via reweighted averages along a single trajectory and kinetic rates are accessed at no additional cost. These abilities are illustrated analyzing a model potential and the umbrella inversion of NH_{3} in water. The algorithm allows a parallel implementation and promises to be a powerful tool for the study of rare events.

  • Frequency adaptive Metadynamics for the calculation of rare-event kinetics
    The Journal of chemical physics, 2018
    Co-Authors: Yong Wang, Michele Parrinello, Pratyush Tiwary, Omar Valsson, Kresten Lindorff-larsen
    Abstract:

    The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in contrast to free energies, depend on the route taken. For this reason, specific enhanced sampling methods are needed to calculate long-time scale kinetics. It has recently been demonstrated that it is possible to recover kinetics through the so-called “infrequent Metadynamics” simulations, where the simulations are biased in a way that minimally corrupts the dynamics of moving between metastable states. This method, however, requires the bias to be added slowly, thus hampering applications to processes with only modest separations of time scales. Here we present a frequency-adaptive strategy which bridges normal and infrequent Metadynamics. We show that this strategy can improve the precision and accuracy of rate calculations at fixed computational cost and should be able to extend rate calculations for much slower kinetic processes.The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in contrast to free energies, depend on the route taken. For this reason, specific enhanced sampling methods are needed to calculate long-time scale kinetics. It has recently been demonstrated that it is possible to recover kinetics through the so-called “infrequent Metadynamics” simulations, where the simulations are biased in a way that minimally corrupts the dynamics of moving between metastable states. This method, however, requires the bias to be added slowly, thus hampering applications to processes with only modest separations of time scales. Here we present a frequency-adaptive strategy which bridges normal and infrequent Metadynamics. We show that this strategy can improve the precision and accuracy of rate calculations at fixed computational cost and should be a...

  • frequency adaptive Metadynamics for the calculation of rare event kinetics
    arXiv: Chemical Physics, 2018
    Co-Authors: Yong Wang, Michele Parrinello, Pratyush Tiwary, Omar Valsson, Kresten Lindorfflarsen
    Abstract:

    The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in contrast to free energies, depend on the route taken and are thus not amenable to all enhanced sampling methods. It has recently been demonstrated that it is possible to recover kinetics through so called `infrequent Metadynamics' simulations, where the simulations are biased in a way that minimally corrupts the dynamics of moving between metastable states. This method, however, requires the bias to be added slowly, thus hampering applications to processes with only modest separations of timescales. Here we present a frequency-adaptive strategy which bridges normal and infrequent Metadynamics. We show that this strategy can improve the precision and accuracy of rate calculations at fixed computational cost, and should be able to extend rate calculations for much slower kinetic processes.

  • a variational conformational dynamics approach to the selection of collective variables in Metadynamics
    arXiv: Statistical Mechanics, 2017
    Co-Authors: Michele Parrinello, James Mccarty
    Abstract:

    In this paper we combine two powerful computational techniques, well-tempered Metadynamics and time lagged independent component analysis. The aim is to develop a new tool for studying rare events and exploring complex free energy landscapes. Metadynamics is a well-established and widely used enhanced sampling method whose efficiency depends on an appropriate choice of collective variables. Often the initial choice is not optimal leading to slow convergence. However by analyzing the dynamics generated in one such a run with a time-lagged independent component analysis and the techniques recently developed in the area of conformational dynamics, we obtain much more efficient collective variables, that are also better capable of illuminating the physics of the system. We demonstrate the power of this approach in two paradigmatic examples.

  • A perturbative solution to Metadynamics ordinary differential equation
    Journal of Chemical Physics, 2015
    Co-Authors: Pratyush Tiwary, James F. Dama, Michele Parrinello
    Abstract:

    Metadynamics is a popular enhanced sampling scheme wherein by periodic application of a repulsive bias, one can surmount high free energy barriers and explore complex landscapes. Recently Metadynamics was shown to be mathematically well founded, in the sense that the biasing procedure is guaranteed to converge to the true free energy surface in the long time limit irrespective of the precise choice of biasing parameters. A differential equation governing the post-transient convergence behavior of Metadynamics was also derived. In this short communication, we revisit this differential equation, expressing it in a convenient and elegant Riccati-like form. A perturbative solution scheme is then developed for solving this differential equation, which is valid for any generic biasing kernel. The solution clearly demonstrates the robustness of Metadynamics to choice of biasing parameters and gives further confidence in the widely used method.

Thomas Vogel - One of the best experts on this subject based on the ideXlab platform.

Massimiliano Bonomi - One of the best experts on this subject based on the ideXlab platform.

  • a practical guide to the simultaneous determination of protein structure and dynamics using metainference
    Methods of Molecular Biology, 2019
    Co-Authors: Thomas Löhr, Carlo Camilloni, Massimiliano Bonomi, Michele Vendruscolo
    Abstract:

    Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well as with system heterogeneity. Furthermore, metainference can be implemented using the Metadynamics approach, which enables the computational study of complex biological systems requiring extensive conformational sampling. In this chapter, we provide a step-by-step guide to perform and analyse Metadynamic metainference simulations using the ISDB module of the open-source PLUMED library, as well as a series of practical tips to avoid common mistakes. Specifically, we will guide the reader in the process of learning how to model the structural ensemble of a small disordered peptide by combining state-of-the-art molecular mechanics force fields with nuclear magnetic resonance data, including chemical shifts, scalar couplings and residual dipolar couplings.

  • Metadynamic metainference: Enhanced sampling of the metainference ensemble using Metadynamics.
    Scientific reports, 2016
    Co-Authors: Massimiliano Bonomi, Carlo Camilloni, Michele Vendruscolo
    Abstract:

    Accurate and precise structural ensembles of proteins and macromolecular complexes can be obtained with metainference, a recently proposed Bayesian inference method that integrates experimental information with prior knowledge and deals with all sources of errors in the data as well as with sample heterogeneity. The study of complex macromolecular systems, however, requires an extensive conformational sampling, which represents a separate challenge. To address such challenge and to exhaustively and efficiently generate structural ensembles we combine metainference with Metadynamics and illustrate its application to the calculation of the free energy landscape of the alanine dipeptide.

  • Efficient Sampling of High-Dimensional Free-Energy Landscapes with Parallel Bias Metadynamics.
    Journal of chemical theory and computation, 2015
    Co-Authors: Jim Pfaendtner, Massimiliano Bonomi
    Abstract:

    Metadynamics accelerates sampling of molecular dynamics while reconstructing thermodynamic properties of selected descriptors of the system. Its main practical difficulty originates from the compromise between keeping the number of descriptors small for efficiently exploring their multidimensional free-energy landscape and biasing all of the slow motions of a process. Here we illustrate on a model system and on the tryptophan-cage miniprotein parallel bias Metadynamics, a method that overcomes this issue by simultaneously applying multiple low-dimensional bias potentials.

  • Funnel Metadynamics as accurate binding free-energy method
    Proceedings of the National Academy of Sciences of the United States of America, 2013
    Co-Authors: Vittorio Limongelli, Massimiliano Bonomi, Michele Parrinello
    Abstract:

    A detailed description of the events ruling ligand/protein interaction and an accurate estimation of the drug affinity to its target is of great help in speeding drug discovery strategies. We have developed a Metadynamics-based approach, named funnel Metadynamics, that allows the ligand to enhance the sampling of the target binding sites and its solvated states. This method leads to an efficient characterization of the binding free-energy surface and an accurate calculation of the absolute protein–ligand binding free energy. We illustrate our protocol in two systems, benzamidine/trypsin and SC-558/cyclooxygenase 2. In both cases, the X-ray conformation has been found as the lowest free-energy pose, and the computed protein–ligand binding free energy in good agreement with experiments. Furthermore, funnel Metadynamics unveils important information about the binding process, such as the presence of alternative binding modes and the role of waters. The results achieved at an affordable computational cost make funnel Metadynamics a valuable method for drug discovery and for dealing with a variety of problems in chemistry, physics, and material science.

  • reconstructing the equilibrium boltzmann distribution from well tempered Metadynamics
    Journal of Computational Chemistry, 2009
    Co-Authors: Massimiliano Bonomi, Alessandro Barducci, Michele Parrinello
    Abstract:

    Metadynamics is a widely used and successful method for reconstructing the free-energy surface of complex systems as a function of a small number of suitably chosen collective variables. This is achieved by biasing the dynamics of the system. The bias acting on the collective variables distorts the probability distribution of the other variables. Here we present a simple reweighting algorithm for recovering the unbiased probability distribution of any variable from a well-tempered Metadynamics simulation. We show the efficiency of the reweighting procedure by reconstructing the distribution of the four backbone dihedral angles of alanine dipeptide from two and even one dimensional Metadynamics simulation. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009

Elena V. Pereloma - One of the best experts on this subject based on the ideXlab platform.

  • the effect of nb solute and nbc precipitates on dynamic and Metadynamic recrystallisation in ni 30fe nb c model alloys
    Materials Science and Engineering A-structural Materials Properties Microstructure and Processing, 2017
    Co-Authors: Parvez Mannan, Gilberto Casillas, Elena V. Pereloma
    Abstract:

    Abstract Dynamic and Metadynamic recrystallisation behaviour of Ni-30Fe-Nb-C model alloys during plane strain compression was investigated by optical and electron microscopy. The dynamically recrystallised grains were primarily located at the pre-existing grain boundaries with few additional new recrystallised grains in the prior grain interior. A limited nucleation of recrystallised grains at >400 nm size NbC particles was also evident. On the other hand, smaller semi-coherent particles (~10–150 nm) severely inhibit the dislocations rearrangement and subgrain boundary mobility, thus leading to sluggish or even suppressed dynamic and Metadynamic recrystallisation. These smaller NbC particles maintained cube-on-cube orientation relationship with austenite matrix ( 001 ) NbC || ( 001 ) γ , [ 001 ] NbC || [ 001 ] γ . The shape of the NbC particles changes from nearly ellipsoidal to octahedral followed by hexagonal and tetra-kai-decahedral by truncation of { 111 } facets by { 001 } ones.

  • particle stimulated nucleation during dynamic and Metadynamic recrystallisation of ni 30 fe nb c alloy
    Materials Characterization, 2017
    Co-Authors: Elena V. Pereloma, Parvez Mannan, Gilberto Casillas, Ahmed A. Saleh
    Abstract:

    Abstract For the first time, a combination of scanning transmission electron microscopy and electron back-scattering diffraction is used to elucidate the early stages of particle stimulated recrystallisation at Nb carbides in Ni-30wt.%Fe alloy subjected to high temperature plane strain compression. While particles with sizes even below 1 μm were found to induce dynamic or Metadynamic recrystallisation, only a small fraction of coarse particles served as nucleation sites.

  • Particle stimulated nucleation during dynamic and Metadynamic recrystallisation of Ni-30%Fe-Nb-C alloy
    Materials Characterization, 2017
    Co-Authors: Elena V. Pereloma, Parvez Mannan, Gilberto Casillas, Ahmed A. Saleh
    Abstract:

    Abstract For the first time, a combination of scanning transmission electron microscopy and electron back-scattering diffraction is used to elucidate the early stages of particle stimulated recrystallisation at Nb carbides in Ni-30wt.%Fe alloy subjected to high temperature plane strain compression. While particles with sizes even below 1 μm were found to induce dynamic or Metadynamic recrystallisation, only a small fraction of coarse particles served as nucleation sites.

Jeanmarc Lancelin - One of the best experts on this subject based on the ideXlab platform.

  • predicting and understanding the enzymatic inhibition of human peroxiredoxin 5 by 4 substituted pyrocatechols by combining funnel Metadynamics solution nmr and steady state kinetics
    Biochemistry, 2016
    Co-Authors: Melissa L Chow, Laura Troussicot, Marie Martin, Bastien Doumeche, Florence Guilliere, Jeanmarc Lancelin
    Abstract:

    Funnel Metadynamics is a kind of computational simulation used to enhance the sampling of protein–ligand binding events in solution. By characterization of the binding interaction events, an estimated absolute binding free energy can be calculated. Nuclear magnetic resonance and funnel Metadynamics were used to evaluate the binding of pyrocatechol derivatives (catechol, 4-methylcatechol, and 4-tert-butylcatechol) to human peroxiredoxin 5. Human peroxiredoxins are peroxidases involved in cellular peroxide homeostasis. Recently, overexpressed or suppressed peroxiredoxin levels have been linked to various diseases. Here, the catechol derivatives were found to be inhibitors against human peroxiredoxin 5 through a partial mixed type noncompetitive mechanism. Funnel Metadynamics provided a microscopic model for interpreting the inhibition mechanism. Correlations were observed between the inhibition constants and the absolute binding free energy. Overall, this study showcases the fact that funnel Metadynamics si...

  • Predicting and Understanding the Enzymatic Inhibition of Human Peroxiredoxin 5 by 4‑Substituted Pyrocatechols by Combining Funnel Metadynamics, Solution NMR, and Steady-State Kinetics
    2016
    Co-Authors: Melissa L. Chow, Laura Troussicot, Marie Martin, Bastien Doumèche, Florence Guillière, Jeanmarc Lancelin
    Abstract:

    Funnel Metadynamics is a kind of computational simulation used to enhance the sampling of protein–ligand binding events in solution. By characterization of the binding interaction events, an estimated absolute binding free energy can be calculated. Nuclear magnetic resonance and funnel Metadynamics were used to evaluate the binding of pyrocatechol derivatives (catechol, 4-methylcatechol, and 4-tert-butylcatechol) to human peroxiredoxin 5. Human peroxiredoxins are peroxidases involved in cellular peroxide homeostasis. Recently, overexpressed or suppressed peroxiredoxin levels have been linked to various diseases. Here, the catechol derivatives were found to be inhibitors against human peroxiredoxin 5 through a partial mixed type noncompetitive mechanism. Funnel Metadynamics provided a microscopic model for interpreting the inhibition mechanism. Correlations were observed between the inhibition constants and the absolute binding free energy. Overall, this study showcases the fact that funnel Metadynamics simulations can be employed as a preliminary approach to gain an in-depth understanding of potential enzyme inhibitors