Folding of the GB1 hairpin peptide from discrete path sampling

Evans, David A.; Wales, David J.

doi:10.1063/1.1759317

Cited by 133 publications

(168 citation statements)

References 48 publications

(80 reference statements)

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“…The kinetics between the nodes can be recovered by a master equation 1 Carlo (KMC) methods. [5][6][7][8][9] KMC is particularly suitable for situations in which the time scale separation between different motions of interest is large, such as in protein folding. TNs have found several applications in protein folding, [10][11][12][13][14][15][16][17][18] enzyme catalysis, 19,20 ligand migration, 21 and studies of electron spin resonance.…”

Section: Introductionmentioning

confidence: 99%

A comparative analysis of clustering algorithms: O2 migration in truncated hemoglobin I from transition networks

Cazade

Zheng

Prada‐Gracia

et al. 2015

The Journal of Chemical Physics

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The ligand migration network for O2–diffusion in truncated Hemoglobin N is analyzed based on three different clustering schemes. For coordinate-based clustering, the conventional k–means and the kinetics-based Markov Clustering (MCL) methods are employed, whereas the locally scaled diffusion map (LSDMap) method is a collective-variable-based approach. It is found that all three methods agree well in their geometrical definition of the most important docking site, and all experimentally known docking sites are recovered by all three methods. Also, for most of the states, their population coincides quite favourably, whereas the kinetics of and between the states differs. One of the major differences between k–means and MCL clustering on the one hand and LSDMap on the other is that the latter finds one large primary cluster containing the Xe1a, IS1, and ENT states. This is related to the fact that the motion within the state occurs on similar time scales, whereas structurally the state is found to be quite diverse. In agreement with previous explicit atomistic simulations, the Xe3 pocket is found to be a highly dynamical site which points to its potential role as a hub in the network. This is also highlighted in the fact that LSDMap cannot identify this state. First passage time distributions from MCL clusterings using a one- (ligand-position) and two-dimensional (ligand-position and protein-structure) descriptor suggest that ligand- and protein-motions are coupled. The benefits and drawbacks of the three methods are discussed in a comparative fashion and highlight that depending on the questions at hand the best-performing method for a particular data set may differ.

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Section: Introductionmentioning

confidence: 99%

A comparative analysis of clustering algorithms: O2 migration in truncated hemoglobin I from transition networks

Cazade

Zheng

Prada‐Gracia

et al. 2015

The Journal of Chemical Physics

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“…This approach is particularly well suited for reduced lattice models (10, 11). Similar schemes have been constructed based on the output of more conventional MD simulations (often after clustering or choosing a reaction coordinate) (26,(28)(29)(30)(31) or based on an analysis of the minima and͞or saddle points of the energy surface (27,32,33).We present an approach to the study of protein folding pathways that makes use of the combined power of REMD and a network model for kinetics. REMD simulations are used to generate a ''lattice'' of states by using a modern all-atom effective potential function including implicit solvent that was previously found to correctly identify the native structure for well studied protein folding model systems (21).…”

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confidence: 99%

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confidence: 99%

Protein folding pathways from replica exchange simulations and a kinetic network model

Andrec

Felts

Gallicchio

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

138

167

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We present an approach to the study of protein folding that uses the combined power of replica exchange simulations and a network model for the kinetics. We carry out replica exchange simulations to generate a large (Ϸ10 6 ) set of states with an all-atom effective potential function and construct a kinetic model for folding, using an ansatz that allows kinetic transitions between states based on structural similarity. We use this network to perform random walks in the state space and examine the overall network structure. Results are presented for the C-terminal peptide from the B1 domain of protein G. The kinetics is two-state after small temperature perturbations. However, the coil-to-hairpin folding is dominated by pathways that visit metastable helical conformations. We propose possible mechanisms for the ␣-helix͞ ␤-hairpin interconversion.graph ͉ master equation ͉ protein G P rotein folding is a fundamental problem in modern structural biology, and recent advances in experimental techniques have helped to elucidate some of the thermodynamic and kinetic features that underlie different stages of the folding process (1-3). Computer simulations using reduced (4-11) and atomistic molecular models (12-21) have played a central role in the interpretation of experimental studies. Although reduced models have provided considerable insight into the overall mechanisms of protein folding, especially in helping to clarify the nature of folding funnels, intermediates, and kinetic bottlenecks, they are limited in their ability to explore the detailed molecular aspects of folding. However, because of the large number of degrees of freedom and the rarity of folding events even in small model systems, all-atom simulations require both considerable computational resources and ingenuity to obtain meaningful results; a variety of methods have been developed to increase simulation efficiency.A particularly powerful technique for the calculation of free energy surfaces and other thermodynamic properties of complex systems is replica exchange molecular dynamics (REMD) (22), in which a generalized ensemble of the system is simulated in parallel over a range of temperatures. Periodically, coordinates are exchanged by using a Metropolis criterion that ensures that at any given temperature a canonical distribution is realized and allows for more efficient barrier crossing than could be obtained with conventional simulation methods. Although REMD is a powerful method for exploring free energy landscapes, it does not provide direct information about kinetics. To study folding by using all-atom effective potentials, heterogeneous distributed computing (16,19) and transition path sampling (23, 24) techniques have been used. Although the former can enhance sampling by combining information from a large number of short MD trajectories ''steered'' by rare events, these techniques can introduce a bias toward fast events in the ensemble average of the reactive trajectories (25). Transition path sampling (23,24) can yield quantitative estimat...

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“…Complex network analysis methods, which initially have been inspired by social and computer sciences (e.g. analysis of friendship networks or the World Wide Web [17,18]), have proven to be very useful to understand protein conformational changes in general [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

The OH stretch vibration of liquid water reveals hydrogen-bond clusters

Garrett-Roe

Hamm

2010

Phys. Chem. Chem. Phys.

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There is still an open debate regarding the structure forming capabilities of water at ambient conditions. In order to probe the presence of such inhomogeneities, we apply complex networks analysis methods to a molecular dynamics simulation at room temperature. This study provides both a structural and quantitative characterization of kinetically homogeneous substates present in bulk water. We find that the conformation-space-network is highly modular, and that structural properties of water molecules are spatially correlated over at least two solvation shells. From a kinetic point of view, the free energy surface is characterized by multiple heterogeneous metastable regions with different populations and marginal barriers separating them. The typical timescale of hopping between them is 200-400 fs. A scanning in temperature reveals that those substates can be stabilized either entropically or enthalpically. The latter resembles an ice-like domain that extends for at least two solvation shells.

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Folding of the GB1 hairpin peptide from discrete path sampling

Cited by 133 publications

References 48 publications

A comparative analysis of clustering algorithms: O2 migration in truncated hemoglobin I from transition networks

A comparative analysis of clustering algorithms: O2 migration in truncated hemoglobin I from transition networks

Protein folding pathways from replica exchange simulations and a kinetic network model

The OH stretch vibration of liquid water reveals hydrogen-bond clusters

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