A scalable algorithm to order and annotate continuous observations reveals the metastable states visited by dynamical systems

Blöchliger, Nicolas; Vitalis, Andreas; Caflisch, Amedeo

doi:10.1016/j.cpc.2013.06.009

Cited by 25 publications

(74 citation statements)

References 46 publications

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“…In the present, short contribution, we apply the method of Blöchliger et al 9. to two molecular dynamics trajectories of proteins, which were produced using dedicated hardware11.…”

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confidence: 99%

High-Resolution Visualisation of the States and Pathways Sampled in Molecular Dynamics Simulations

Blöchliger

Vitalis

Caflisch

2014

Sci Rep

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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.

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“…In the present, short contribution, we apply the method of Blöchliger et al 9. to two molecular dynamics trajectories of proteins, which were produced using dedicated hardware11.…”

mentioning

confidence: 99%

High-Resolution Visualisation of the States and Pathways Sampled in Molecular Dynamics Simulations

Blöchliger

Vitalis

Caflisch

2014

Sci Rep

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“…II B for settings). All copies were run for a stretch of a given and fixed length (here, 100 ps), and snapshots sufficient to allow the extraction of the required features (Table I) stretch, all saved snapshots from all replicas were analyzed concurrently by state-of-the-art analysis algorithms 45,46 implemented in CAMPARI (http://campari.sourceforge.net), which are central to the PIGS protocol. Then, new stretches were restarted according to the reseeding decisions made by PIGS.…”

Section: A Pigs Protocolmentioning

confidence: 99%

“…It is an unsupervised analysis method able to reveal different free energy basins and barrier regions explored by a stochastic dynamical system such as a biomolecule in solution. 46 PIGS exploits this information to make reseeding decisions as detailed below. The PI has as its only essential input parameter the choice of features and metric function defining the conformational (geometric) distance between two snapshots, and the choice of features is what we vary in this contribution to achieve a focused exploration.…”

Section: A Pigs Protocolmentioning

confidence: 99%

“…It is designed to fit modern HPC resources as it evolves a constant and possibly large number of replicas of a system in parallel and relies on state-of-the-art scalable analysis algorithms to enhance the sampling. 9,45,46 Unlike in FAST 40 or adaptive sampling, 36 this does not imply building MSMs on-the-fly. In short, PIGS works as follows.…”

Section: Introductionmentioning

confidence: 99%

“…It is these selections that enable PIGS to focus the sampling enhancements in response to specific questions. To accomplish this, all collected snapshots from all replicas are arranged jointly in the so-called progress index (PI), 46 which is analyzed to derive a ranking of the current end points of the simulation stretches in a way that rewards sampling FIG. 1.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Focused conformational sampling in proteins

Bacci

Langini

Vymětal

et al. 2017

The Journal of Chemical Physics

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A detailed understanding of the conformational dynamics of biological molecules is difficult to obtain by experimental techniques due to resolution limitations in both time and space. Computer simulations avoid these in theory but are often too short to sample rare events reliably. Here we show that the progress index-guided sampling (PIGS) protocol can be used to enhance the sampling of rare events in selected parts of biomolecules without perturbing the remainder of the system. The method is very easy to use as it only requires as essential input a set of several features representing the parts of interest sufficiently. In this feature space, new states are discovered by spontaneous fluctuations alone and in unsupervised fashion. Because there are no energetic biases acting on phase space variables or projections thereof, the trajectories PIGS generates can be analyzed directly in the framework of transition networks. We demonstrate the possibility and usefulness of such focused explorations of biomolecules with two loops that are part of the binding sites of bromodomains, a family of epigenetic "reader" modules. This real-life application uncovers states that are structurally and kinetically far away from the initial crystallographic structures and are also metastable. Representative conformations are intended to be used in future high-throughput virtual screening campaigns.

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A molecular simulation protocol to avoid sampling redundancy and discover new states

Bacci

Vitalis

Caflisch

2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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A scalable algorithm to order and annotate continuous observations reveals the metastable states visited by dynamical systems

Cited by 25 publications

References 46 publications

High-Resolution Visualisation of the States and Pathways Sampled in Molecular Dynamics Simulations

High-Resolution Visualisation of the States and Pathways Sampled in Molecular Dynamics Simulations

Focused conformational sampling in proteins

A molecular simulation protocol to avoid sampling redundancy and discover new states

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