Focused conformational sampling in proteins.

@article{Bacci2017FocusedCS,
  title={Focused conformational sampling in proteins.},
  author={Marco Bacci and Cassiano Langini and Jiř{\'i} Vymětal and Amedeo Caflisch and Andreas Vitalis},
  journal={The Journal of chemical physics},
  year={2017},
  volume={147 19},
  pages={
          195102
        }
}
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… 
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7 Citations

7 Citations

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References

SHOWING 1-10 OF 89 REFERENCES
A molecular simulation protocol to avoid sampling redundancy and discover new states.
WExplore: hierarchical exploration of high-dimensional spaces using the weighted ensemble algorithm.
TLDR
This work presents a novel strategy to determine structural ensembles that uses dynamically defined sampling regions that are organized in a hierarchical framework based on the weighted ensemble algorithm, where an ensemble of copies of the system is directed to new regions of configuration space through merging and cloning operations.
Rapid equilibrium sampling initiated from nonequilibrium data
TLDR
The adaptive seeding method (ASM), which uses nonequilibrium GE simulations to identify the metastable states, and seeds short simulations at constant temperature from each of them to quantitatively determine their equilibrium populations, and is well suited to running on modern computer clusters.
Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin
TLDR
This work studies a large-scale transition in a united-residue model of calmodulin using the “weighted ensemble” (THE AUTHORS) approach of Huber and Kim, and indicates that the THEY approach quantitatively reproduces the brute-force results.
Will molecular dynamics simulations of proteins ever reach equilibrium?
We show that conformational entropies calculated for five proteins and protein-ligand complexes with dihedral-distribution histogramming, the von Mises approach, or quasi-harmonic analysis do not…
Path-sampling strategies for simulating rare events in biomolecular systems.
FAST Conformational Searches by Balancing Exploration/Exploitation Trade-Offs.
TLDR
A goal-oriented sampling method, called fluctuation amplification of specific traits (FAST), for extending the capabilities of commodity hardware by outperforming conventional simulations and an adaptive sampling algorithm by at least an order of magnitude.
50 Years of Lifson-Roig Models: Application to Molecular Simulation Data.
TLDR
A simple variant of the Lifson-Roig model is designed that recovers physical interpretability of the obtained parameters by allowing bundle formation to be described in simple fashion, and it is shown that enthalpies of helix formation are more robustly determined using van't Hoff analysis of simple measures of helicity rather than fitted propagation parameters.
Biomolecular modeling and simulation: a field coming of age
TLDR
Despite early unrealistic expectations and the realization that computer technology alone will not quickly bridge the gap between experimental and theoretical time frames, ongoing improvements to enhance the accuracy and scope of modeling and simulation are propelling the field onto a productive trajectory.
Efficient Construction of Mesostate Networks from Molecular Dynamics Trajectories.
TLDR
A tree-based algorithm to partition conformations of biomolecules into sets of similar microstates, i.e., to coarse-grain trajectory data into mesostates is presented and it is demonstrated that the derived mesostate networks can preserve information regarding the free energy basins and barriers by which the system is characterized.
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