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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 FiP35.(a) The progress index, of 106 snapshots from 200 μs of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (red dots), DSSP assignment17 by residue (legend on top) and the state partitioning of Berezovska et al.20 These annotations are only shown for every 1000th, 100th, 1000th and 500th snapshots, respectively, in order to maintain readability at fixed figure resolution. The limits of possible definitions of the folded and unfolded states for the computation of transition path times are indicated by the blue, horizontal lines. Cartoons31 of a snapshot in the native state and an unfolded conformation are shown. (b) Zoom-in on the transition region of the SAPPHIRE plot shown in (a). The various annotations are shown for every 100th, 10th, 50th, and 250th snapshots, respectively. Representative conformations of I1 and I2 are shown as cartoons. The box highlights a particular state (see text).
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f1: SAPPHIRE plot for FiP35.(a) The progress index, of 106 snapshots from 200 μs of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (red dots), DSSP assignment17 by residue (legend on top) and the state partitioning of Berezovska et al.20 These annotations are only shown for every 1000th, 100th, 1000th and 500th snapshots, respectively, in order to maintain readability at fixed figure resolution. The limits of possible definitions of the folded and unfolded states for the computation of transition path times are indicated by the blue, horizontal lines. Cartoons31 of a snapshot in the native state and an unfolded conformation are shown. (b) Zoom-in on the transition region of the SAPPHIRE plot shown in (a). The various annotations are shown for every 100th, 10th, 50th, and 250th snapshots, respectively. Representative conformations of I1 and I2 are shown as cartoons. The box highlights a particular state (see text).

Mentions: FiP3512 exhibits reversible folding at a simulation temperature of 395 K in explicit solvent molecular dynamics runs of a total length of 200 μs. Specifically, the trajectories show that FiP35 converts 10–15 times between an unfolded state that is very low in secondary structure content and the native topology, viz., a twisted, three-stranded β-sheet111516. All following results refer to a specific computational model and sampling protocol11 underlying the trajectories being analysed. Due to the protein's small size, it is possible to provide a comprehensive, structural representation at the backbone level using a DSSP annotation17 resolved by residue. Fig. 1(a) shows the SAPPHIRE plot for the composite trajectory using this annotation, and it is immediately apparent that the native topology is observed more than 50% of the time. The native basin is delineated by the kinetic annotation (black line) as expected. The unfolded state shows no consistent secondary structure and is kinetically homogeneous, suggesting that FiP35 should be described well as a two-state folder.


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 FiP35.(a) The progress index, of 106 snapshots from 200 μs of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (red dots), DSSP assignment17 by residue (legend on top) and the state partitioning of Berezovska et al.20 These annotations are only shown for every 1000th, 100th, 1000th and 500th snapshots, respectively, in order to maintain readability at fixed figure resolution. The limits of possible definitions of the folded and unfolded states for the computation of transition path times are indicated by the blue, horizontal lines. Cartoons31 of a snapshot in the native state and an unfolded conformation are shown. (b) Zoom-in on the transition region of the SAPPHIRE plot shown in (a). The various annotations are shown for every 100th, 10th, 50th, and 250th snapshots, respectively. Representative conformations of I1 and I2 are shown as cartoons. The box highlights a particular state (see text).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: SAPPHIRE plot for FiP35.(a) The progress index, of 106 snapshots from 200 μs of MD data, is annotated with kinetic information (τMFP, black curve), dynamical trace (red dots), DSSP assignment17 by residue (legend on top) and the state partitioning of Berezovska et al.20 These annotations are only shown for every 1000th, 100th, 1000th and 500th snapshots, respectively, in order to maintain readability at fixed figure resolution. The limits of possible definitions of the folded and unfolded states for the computation of transition path times are indicated by the blue, horizontal lines. Cartoons31 of a snapshot in the native state and an unfolded conformation are shown. (b) Zoom-in on the transition region of the SAPPHIRE plot shown in (a). The various annotations are shown for every 100th, 10th, 50th, and 250th snapshots, respectively. Representative conformations of I1 and I2 are shown as cartoons. The box highlights a particular state (see text).
Mentions: FiP3512 exhibits reversible folding at a simulation temperature of 395 K in explicit solvent molecular dynamics runs of a total length of 200 μs. Specifically, the trajectories show that FiP35 converts 10–15 times between an unfolded state that is very low in secondary structure content and the native topology, viz., a twisted, three-stranded β-sheet111516. All following results refer to a specific computational model and sampling protocol11 underlying the trajectories being analysed. Due to the protein's small size, it is possible to provide a comprehensive, structural representation at the backbone level using a DSSP annotation17 resolved by residue. Fig. 1(a) shows the SAPPHIRE plot for the composite trajectory using this annotation, and it is immediately apparent that the native topology is observed more than 50% of the time. The native basin is delineated by the kinetic annotation (black line) as expected. The unfolded state shows no consistent secondary structure and is kinetically homogeneous, suggesting that FiP35 should be described well as a two-state folder.

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