Metastable state identification

[maxentile]

How can we efficiently identify metastable states?

• Specifically, can protein design algorithms be used? http://www.cs.duke.edu/donaldlab/osprey.php

John Chodera suggests:

• Multistate transition interface sampling: http://www.ncbi.nlm.nih.gov/pubmed/23901958
• Hierarchical uncoupling-coupling Monte Carlo: http://link.springer.com/chapter/10.1007%2F978-3-642-56080-4_10
• Grid-free hierarchical conformational dynamics: http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000008079 Statistical Error Estimation and Grid-free Hierarchical Refinement in Conformation Dynamics.
• TRAM and dynamical reweighting:
  • http://www.choderalab.org/publications/2014/4/26/optimal-use-of-data-in-parallel-tempering-simulations-for-the-construction-of-discrete-state-markov-models-of-biomolecular-dynamics?rq=prinz
  • http://arxiv.org/abs/1407.0138
• Metadynamics and related schemes: "Schemes like metadynamics (Danny knows much more about this) can modify the dynamics significantly to "push" the simulation into new regions of space, but usually require some knowledge of relevant order parameters to do this. We've always wondered if simply using repulsive "hills" in RMSD to already-visited configurations may be sufficient to encourage the system to explore new conformations and metastable states, though it's not obvious how one would correct for this to get an initial estimate of transition rates among states or even state boundaries."