## Robust Density-Based Clustering To Identify Metastable Conformational States of Proteins

journal contribution

posted on 08.04.2016 by Florian Sittel, Gerhard Stock#### journal contribution

Any type of content formally published in an academic journal, usually following a peer-review process.

A density-based clustering
method is proposed that is deterministic,
computationally efficient, and self-consistent in its parameter choice.
By calculating a geometric coordinate space density for every point
of a given data set, a local free energy is defined. On the basis
of these free energy estimates, the frames are lumped into local free
energy minima, ultimately forming microstates separated by local free
energy barriers. The algorithm is embedded into a complete workflow
to robustly generate Markov state models from molecular dynamics trajectories.
It consists of (i) preprocessing of the data via principal component
analysis in order to reduce the dimensionality of the problem, (ii)
proposed density-based clustering to generate microstates, and (iii)
dynamical clustering via the

*most probable path*algorithm to construct metastable states. To characterize the resulting state-resolved conformational distribution, dihedral angle content color plots are introduced which identify structural differences of protein states in a concise way. To illustrate the performance of the method, three well-established model problems are adopted: conformational transitions of hepta-alanine, folding of villin headpiece, and functional dynamics of bovine pancreatic trypsin inhibitor.#### Read the peer-reviewed publication

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dynamics trajectoriesprotein statesenergy barriersparameter choicespace densityMarkov state modelsmodel problemsmethodmetastable statescomponent analysismicrostateIdentify Metastable Conformational Statesvillin headpieceenergy estimatesdatadihedral angle content color plotsenergy minimapath algorithmpancreatic trypsin inhibitor

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#### Read the peer-reviewed publication

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### Keyword(s)

dynamics trajectoriesprotein statesenergy barriersparameter choicespace densityMarkov state modelsmodel problemsmethodmetastable statescomponent analysismicrostateIdentify Metastable Conformational Statesvillin headpieceenergy estimatesdatadihedral angle content color plotsenergy minimapath algorithmpancreatic trypsin inhibitor