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Protein folding is mechanistically robust.

ABSTRACT: Markov state models (MSMs) have proven to be useful tools in simulating large and slowly-relaxing biological systems like proteins. MSMs model proteins through dynamics on a discrete-state energy landscape, allowing molecules to effectively sample large regions of phase space. In this work, we use aspects of MSMs to ask: is protein folding mechanistically robust? We first provide a definition of mechanism in the context of Markovian models, and we later use perturbation theory and the concept of parametric sloppiness to show that parts of the MSM eigenspectrum are resistant to perturbation. We introduce a new, to our knowledge, Bayesian metric by which eigenspectrum robustness can be evaluated, and we discuss the implications of mechanistic robustness and possible new applications of MSMs to understanding biophysical phenomena.

SUBMITTER: Weber JK 

PROVIDER: S-EPMC3283819 | biostudies-other | 2012 Feb

REPOSITORIES: biostudies-other

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Protein folding is mechanistically robust.

Weber Jeffrey K JK   Pande Vijay S VS  

Biophysical journal 20120221 4

Markov state models (MSMs) have proven to be useful tools in simulating large and slowly-relaxing biological systems like proteins. MSMs model proteins through dynamics on a discrete-state energy landscape, allowing molecules to effectively sample large regions of phase space. In this work, we use aspects of MSMs to ask: is protein folding mechanistically robust? We first provide a definition of mechanism in the context of Markovian models, and we later use perturbation theory and the concept of  ...[more]