Prediction of protein conformational freedom from distance constraints

Groot, Bert L. de; Aalten, Daan M. F. van; Scheek, Ruud M.; Amadei, Andrea; Vriend, Gerrit; Berendsen, H.J.C.

doi:10.1002/(sici)1097-0134(199710)29:2<240::aid-prot11>3.0.co;2-o

Cited by 256 publications

(287 citation statements)

References 47 publications

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“…The notion that internal constraints and other con®gurational barriers restrict protein dynamics to a limited number of collective degrees of freedom has led to the design of the CON-COORD method to predict these modes without doing explicit MD simulations. The CONCOORD method has been described in detail elsewhere (De Groot et al, 1997) and will only be summarised brie¯y here, together with some recent modi®cations.…”

Section: Concoord Simulationsmentioning

confidence: 99%

“…Since the ®rst implementation of CONCOORD (De Groot et al, 1997), a number of improvements have been made. { First, the original algorithm which required all distances to be restricted has been modi®ed to make the method suitable for large systems.…”

Section: Concoord Simulationsmentioning

confidence: 99%

“…Ma & Karplus (1998) recently performed normal mode calculations on a minimal subsystem (three subunits) of GroEL that could provide insight into its allosteric mechanism. We have chosen to use CONCOORD (De Groot et al, 1997), which is a method to generate different protein conformations based on distance restrictions. This method has been shown to yield low frequency collective¯uctuations for proteins very similar to those that can be extracted from MD simulations, but at a dramatically reduced computational expense (De Groot et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…We have chosen to use CONCOORD (De Groot et al, 1997), which is a method to generate different protein conformations based on distance restrictions. This method has been shown to yield low frequency collective¯uctuations for proteins very similar to those that can be extracted from MD simulations, but at a dramatically reduced computational expense (De Groot et al, 1997). To study the allosteric mechanism of GroEL, CONCOORD simulations have been performed of complete GroEL and GroEL/GroES assemblies starting from the different experimentally determined GroEL conformations.…”

Section: Introductionmentioning

confidence: 99%

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Conformational changes in the chaperonin GroEL: new insights into the allosteric mechanism 1 1Edited by A. R. Fersht

Groot

Vriend

Berendsen

1999

Journal of Molecular Biology

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Conformational changes are known to play a crucial role in the function of the bacterial GroE chaperonin system. Here, results are presented from an essential dynamics analysis of known experimental structures and from computer simulations of GroEL using the CONCOORD method. The results indicate a possible direct form of inter-ring communication associated with internal¯uctuations in the nucleotide-binding domains upon nucleotide and GroES binding that are involved in the allosteric mechanism of GroEL. At the level of conformational transitions in entire GroEL rings, nucleotide-induced structural changes were found to be distinct and in principle uncoupled from changes occurring upon GroES binding. However, a coupling is found between nucleotide-induced conformational changes and GroES-mediated transitions, but only in simulations of GroEL double rings, and not in simulations of single rings. This provides another explanation for the fact that GroEL functions a double ring system.

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Section: Concoord Simulationsmentioning

confidence: 99%

Section: Concoord Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Conformational changes in the chaperonin GroEL: new insights into the allosteric mechanism 1 1Edited by A. R. Fersht

Groot

Vriend

Berendsen

1999

Journal of Molecular Biology

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“…28,29 Here, we use the CONCOORD algorithm which exploits information from the experimentally derived structure in combination with a set of predefined geometrical constraints. 30,31 …”

Section: Introductionmentioning

confidence: 99%

Communication: Microsecond peptide dynamics from nanosecond trajectories: A Langevin approach

Rzepiela

Schaudinnus

Buchenberg

et al. 2014

The Journal of Chemical Physics

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Based on a given time series, the data-driven Langevin equation (dLE) estimates the drift and the diffusion field of the dynamics, which are then employed to reproduce the essential statistical and dynamical features of the original time series. Because the propagation of the dLE requires only local information, the input data are neither required to be Boltzmann weighted nor to be a continuous trajectory. Similar to a Markov state model, the dLE approach therefore holds the promise of predicting the long-time dynamics of a biomolecular system from relatively short trajectories which can be run in parallel. The practical applicability of the approach is shown to be mainly limited by the initial sampling of the system's conformational space obtained from the short trajectories. Adopting extensive molecular dynamics simulations of the unfolding and refolding of a short peptide helix, it is shown that the dLE approach is able to describe microsecond conformational dynamics from a few hundred nanosecond trajectories. In particular, the dLE quantitatively reproduces the free energy landscape and the associated conformational dynamics along the chosen five-dimensional reaction coordinate. C 2014 AIP Publishing LLC. [http://dx

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Efficient sampling in collective coordinate space

Abseher

Nilges

2000

Proteins

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Collective motions in biological macromolecules have been shown to be important for function. The most important collective motions occur on slow time scales, which poses a sampling problem in dynamic simulation of biomolecules. We present a novel method for efficient conformational sampling. The method combines the simulation of an ensemble of concurrent trajectories with restraints acting on the ensemble of structures as a whole. Two properties of the ensemble may be restrained: (i) the variance of the ensemble and (ii) the average position of the ensemble. Both properties are defined in a subspace of collective coordinate space spanned by an arbitrary number of modes. We show that weak restraints on the ensemble variance suffice for an increase in sampling efficiency along soft modes by two orders of magnitudes. The resulting trajectories exhibit virtually the same structural quality as trajectories generated by restraint-free-molecular dynamics simulation, as judged by standard structure validation tools. The method is used to probe the resistance of a structure against conformational changes along collective modes and clearly distinguishes soft from stiff modes. Further applications are discussed. Proteins 2000;39:82-88.

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Prediction of protein conformational freedom from distance constraints

Cited by 256 publications

References 47 publications

Conformational changes in the chaperonin GroEL: new insights into the allosteric mechanism 1 1Edited by A. R. Fersht

Conformational changes in the chaperonin GroEL: new insights into the allosteric mechanism 1 1Edited by A. R. Fersht

Communication: Microsecond peptide dynamics from nanosecond trajectories: A Langevin approach

Efficient sampling in collective coordinate space

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