Optimized Markov state models for metastable systems

Enrico Guarnera, Eric Vanden Eijnden

Research output: Contribution to journalArticle

Abstract

A method is proposed to identify target states that optimize a metastability index amongst a set of trial states and use these target states as milestones (or core sets) to build Markov State Models (MSMs). If the optimized metastability index is small, this automatically guarantees the accuracy of the MSM, in the sense that the transitions between the target milestones is indeed approximately Markovian. The method is simple to implement and use, it does not require that the dynamics on the trial milestones be Markovian, and it also offers the possibility to partition the system's state-space by assigning every trial milestone to the target milestones it is most likely to visit next and to identify transition state regions. Here the method is tested on the Gly-Ala-Gly peptide, where it is shown to correctly identify the expected metastable states in the dihedral angle space of the molecule without a priori information about these states. It is also applied to analyze the folding landscape of the Beta3s mini-protein, where it is shown to identify the folded basin as a connecting hub between an helix-rich region, which is entropically stabilized, and a beta-rich region, which is energetically stabilized and acts as a kinetic trap.

Original languageEnglish (US)
Article number024102
JournalJournal of Chemical Physics
Volume145
Issue number2
DOIs
StatePublished - Jul 14 2016

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metastable state
Dihedral angle
Peptides
Molecules
Kinetics
hubs
helices
folding
peptides
dihedral angle
partitions
Proteins
traps
proteins
kinetics
molecules

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

Cite this

Optimized Markov state models for metastable systems. / Guarnera, Enrico; Vanden Eijnden, Eric.

In: Journal of Chemical Physics, Vol. 145, No. 2, 024102, 14.07.2016.

Research output: Contribution to journalArticle

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