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High-resolution visualisation of the states and pathways sampled in molecular dynamics simulations.

Blöchliger N, Vitalis A, Caflisch A - Sci Rep (2014)

Bottom Line: The profile is supplemented by a trace of the temporal evolution of the system highlighting the sequence of events.We demonstrate that the resultant SAPPHIRE (States And Pathways Projected with HIgh REsolution) plots provide a comprehensive picture of the thermodynamics and kinetics of complex, molecular systems exhibiting dynamics covering a range of time and length scales.This minimizes the risk of missing states because of overlap or prior coarse-graining of the data.

View Article: PubMed Central - PubMed

Affiliation: University of Zurich, Department of Biochemistry, Winterthurerstrasse 190, CH-8057 Zurich.

ABSTRACT
We have recently developed a scalable algorithm for ordering the instantaneous observations of a dynamical system evolving continuously in time. Here, we apply the method to long molecular dynamics trajectories. The procedure requires only a pairwise, geometrical distance as input. Suitable annotations of both structural and kinetic nature reveal the free energy basins visited by biomolecules. The profile is supplemented by a trace of the temporal evolution of the system highlighting the sequence of events. We demonstrate that the resultant SAPPHIRE (States And Pathways Projected with HIgh REsolution) plots provide a comprehensive picture of the thermodynamics and kinetics of complex, molecular systems exhibiting dynamics covering a range of time and length scales. Information on pathways connecting states and the level of recurrence are quickly inferred from the visualisation. The considerable advantages of our approach are speed and resolution: the SAPPHIRE plot is scalable to very large data sets and represents every single snapshot. This minimizes the risk of missing states because of overlap or prior coarse-graining of the data.

No MeSH data available.


Related in: MedlinePlus

SAPPHIRE plot for BPTI.(Upper panel) The progress index, of 41250 snapshots from 1.03 ms of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (dots coloured according to the kinetic clustering of Shaw et al.)11, and selected dihedral angles. These annotations are only shown for every 20th, 2nd and 2nd snapshots, respectively, in order to maintain readability at fixed figure resolution. The annotation with dihedral angles uses binning into up to three bins with boundaries chosen as follows: Cys14 χ1 (−120°, −5°, 120°), Cys14 χ2 (−140°, 0°, 130°), Cys14-Cys38 χ3 (0°, 150°), Cys38 χ2 (−155°, −105°, 120°), Cys38 χ1 (−120°, 0°, 140°), Arg42 ψ (−100°, 75°), and Asp3 φ (0°, 100°). These boundaries were obtained from direct inspection of the individual histograms for each angle. Boxes highlight two brief stretches of the trajectory referred to in the text. (Lower panel) Zoom-in on a thin time slice of the dynamical trace to visualise a particular transition from the red to the black state. End points of this transition are shown as cartoons with Arg1 and Phe4 in a stick-like representation31. The plot is annotated further by the distance between the Cγ atom of Phe4 and the Cδ of Arg1, which is shown for every 5th snapshot.
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f2: SAPPHIRE plot for BPTI.(Upper panel) The progress index, of 41250 snapshots from 1.03 ms of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (dots coloured according to the kinetic clustering of Shaw et al.)11, and selected dihedral angles. These annotations are only shown for every 20th, 2nd and 2nd snapshots, respectively, in order to maintain readability at fixed figure resolution. The annotation with dihedral angles uses binning into up to three bins with boundaries chosen as follows: Cys14 χ1 (−120°, −5°, 120°), Cys14 χ2 (−140°, 0°, 130°), Cys14-Cys38 χ3 (0°, 150°), Cys38 χ2 (−155°, −105°, 120°), Cys38 χ1 (−120°, 0°, 140°), Arg42 ψ (−100°, 75°), and Asp3 φ (0°, 100°). These boundaries were obtained from direct inspection of the individual histograms for each angle. Boxes highlight two brief stretches of the trajectory referred to in the text. (Lower panel) Zoom-in on a thin time slice of the dynamical trace to visualise a particular transition from the red to the black state. End points of this transition are shown as cartoons with Arg1 and Phe4 in a stick-like representation31. The plot is annotated further by the distance between the Cγ atom of Phe4 and the Cδ of Arg1, which is shown for every 5th snapshot.

Mentions: Analyses of MD simulations of the folded state ensemble of the 58-residue bovine pancreatic trypsin inhibitor (BPTI) have revealed that a number of states identified by NMR experiments2526 are populated significantly in the trajectories albeit with inaccurate weights. These metastable states can often be correlated with isomerizations of the disulphide bridges, in particular Cys14-Cys382728. Shaw et al.11 used a stochastic algorithm to obtain a coarse, kinetic clustering of their 1.03 ms MD trajectory of BPTI relying on the autocorrelation of interatomic distances. Empirically, they found that five states with significant populations could be identified reliably. These states were annotated structurally. The most important states (the smaller of the two is the one most resembling the crystal structure) are clearly seen in the SAPPHIRE plot as the first two basins from the left (Fig. 2). The structural annotation we select here confirms that the barrier identified by the kinetic analysis (black line) is related to the isomerization of the disulphide bond Cys14-Cys38. The dynamical trace uses the colour scheme of Shaw et al. (distinguishing the red, blue, green, purple, and black states). It unmasks that both major states are long-lived and that there is a clear separation of time scales with respect to the mixing time within each basin.


High-resolution visualisation of the states and pathways sampled in molecular dynamics simulations.

Blöchliger N, Vitalis A, Caflisch A - Sci Rep (2014)

SAPPHIRE plot for BPTI.(Upper panel) The progress index, of 41250 snapshots from 1.03 ms of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (dots coloured according to the kinetic clustering of Shaw et al.)11, and selected dihedral angles. These annotations are only shown for every 20th, 2nd and 2nd snapshots, respectively, in order to maintain readability at fixed figure resolution. The annotation with dihedral angles uses binning into up to three bins with boundaries chosen as follows: Cys14 χ1 (−120°, −5°, 120°), Cys14 χ2 (−140°, 0°, 130°), Cys14-Cys38 χ3 (0°, 150°), Cys38 χ2 (−155°, −105°, 120°), Cys38 χ1 (−120°, 0°, 140°), Arg42 ψ (−100°, 75°), and Asp3 φ (0°, 100°). These boundaries were obtained from direct inspection of the individual histograms for each angle. Boxes highlight two brief stretches of the trajectory referred to in the text. (Lower panel) Zoom-in on a thin time slice of the dynamical trace to visualise a particular transition from the red to the black state. End points of this transition are shown as cartoons with Arg1 and Phe4 in a stick-like representation31. The plot is annotated further by the distance between the Cγ atom of Phe4 and the Cδ of Arg1, which is shown for every 5th snapshot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151098&req=5

f2: SAPPHIRE plot for BPTI.(Upper panel) The progress index, of 41250 snapshots from 1.03 ms of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (dots coloured according to the kinetic clustering of Shaw et al.)11, and selected dihedral angles. These annotations are only shown for every 20th, 2nd and 2nd snapshots, respectively, in order to maintain readability at fixed figure resolution. The annotation with dihedral angles uses binning into up to three bins with boundaries chosen as follows: Cys14 χ1 (−120°, −5°, 120°), Cys14 χ2 (−140°, 0°, 130°), Cys14-Cys38 χ3 (0°, 150°), Cys38 χ2 (−155°, −105°, 120°), Cys38 χ1 (−120°, 0°, 140°), Arg42 ψ (−100°, 75°), and Asp3 φ (0°, 100°). These boundaries were obtained from direct inspection of the individual histograms for each angle. Boxes highlight two brief stretches of the trajectory referred to in the text. (Lower panel) Zoom-in on a thin time slice of the dynamical trace to visualise a particular transition from the red to the black state. End points of this transition are shown as cartoons with Arg1 and Phe4 in a stick-like representation31. The plot is annotated further by the distance between the Cγ atom of Phe4 and the Cδ of Arg1, which is shown for every 5th snapshot.
Mentions: Analyses of MD simulations of the folded state ensemble of the 58-residue bovine pancreatic trypsin inhibitor (BPTI) have revealed that a number of states identified by NMR experiments2526 are populated significantly in the trajectories albeit with inaccurate weights. These metastable states can often be correlated with isomerizations of the disulphide bridges, in particular Cys14-Cys382728. Shaw et al.11 used a stochastic algorithm to obtain a coarse, kinetic clustering of their 1.03 ms MD trajectory of BPTI relying on the autocorrelation of interatomic distances. Empirically, they found that five states with significant populations could be identified reliably. These states were annotated structurally. The most important states (the smaller of the two is the one most resembling the crystal structure) are clearly seen in the SAPPHIRE plot as the first two basins from the left (Fig. 2). The structural annotation we select here confirms that the barrier identified by the kinetic analysis (black line) is related to the isomerization of the disulphide bond Cys14-Cys38. The dynamical trace uses the colour scheme of Shaw et al. (distinguishing the red, blue, green, purple, and black states). It unmasks that both major states are long-lived and that there is a clear separation of time scales with respect to the mixing time within each basin.

Bottom Line: The profile is supplemented by a trace of the temporal evolution of the system highlighting the sequence of events.We demonstrate that the resultant SAPPHIRE (States And Pathways Projected with HIgh REsolution) plots provide a comprehensive picture of the thermodynamics and kinetics of complex, molecular systems exhibiting dynamics covering a range of time and length scales.This minimizes the risk of missing states because of overlap or prior coarse-graining of the data.

View Article: PubMed Central - PubMed

Affiliation: University of Zurich, Department of Biochemistry, Winterthurerstrasse 190, CH-8057 Zurich.

ABSTRACT
We have recently developed a scalable algorithm for ordering the instantaneous observations of a dynamical system evolving continuously in time. Here, we apply the method to long molecular dynamics trajectories. The procedure requires only a pairwise, geometrical distance as input. Suitable annotations of both structural and kinetic nature reveal the free energy basins visited by biomolecules. The profile is supplemented by a trace of the temporal evolution of the system highlighting the sequence of events. We demonstrate that the resultant SAPPHIRE (States And Pathways Projected with HIgh REsolution) plots provide a comprehensive picture of the thermodynamics and kinetics of complex, molecular systems exhibiting dynamics covering a range of time and length scales. Information on pathways connecting states and the level of recurrence are quickly inferred from the visualisation. The considerable advantages of our approach are speed and resolution: the SAPPHIRE plot is scalable to very large data sets and represents every single snapshot. This minimizes the risk of missing states because of overlap or prior coarse-graining of the data.

No MeSH data available.


Related in: MedlinePlus