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decapitalize all instances of Notebook and fix notebook number typo (addresses #171)
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manuscript/manuscript.tex

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@@ -256,7 +256,7 @@ \subsection{Hidden Markov state models}
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The estimation of an MSM requires the dynamics between microstates to be Markovian.
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However, in case of a poor dimension reduction and/or discretization or short trajectories,
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we cannot anticipate this to be the case.
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We illustrate this point in Notebook~07.
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We illustrate this point in notebook~07.
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An alternative, which is much less sensitive to poor discretization,
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is to estimate a hidden Markov model (HMM)~\cite{hmm-baum-welch-alg,hmm-tutorial,jhp-spectral-rate-theory,noe-proj-hid-msm,bhmm-preprint}.
@@ -279,7 +279,7 @@ \subsection{Hidden Markov state models}
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An HMM estimation always yields a model with a small number of (hidden) states
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where each state is considered to be metastable and,
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thus, the number of hidden states is a new hyper-parameter which needs to be chosen carefully (see Notebook~07).
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thus, the number of hidden states is a new hyper-parameter which needs to be chosen carefully (see notebook~07).
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As the HMMs---like MSMs---approximate the full phase-space dynamics,
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we can similarly compute the metastable kinetics, apply TPT, visualize the network, and obtain physical observables.
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@@ -375,10 +375,10 @@ \subsection{Feature selection}
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Here, we utilize the VAMP-2 score, which maximizes the kinetic variance contained in the features~\cite{kinetic-maps}.
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We should always evaluate the score in a cross-validated manner to ensure that we neither include too few features (under-fitting) or too many features (over-fitting)~\cite{gmrq,vamp-preprint}.
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To choose among three different molecular features reflecting protein structure,
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we compute the (cross-validated) VAMP-2 score (Notebook 00).
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we compute the (cross-validated) VAMP-2 score (notebook 00).
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Although we cannot MSM optimize lag times with a variational score\cite{husic2017note}, such as VAMP-2,
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it is important to ensure that properties that we optimize are robust as a function of lag time.
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Consequently, we compute the VAMP-2 score at several lag times (Notebook 00).
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Consequently, we compute the VAMP-2 score at several lag times (notebook 00).
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We find that the relative rankings of the different molecular features are highly robust as a function of lag time.
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We show one example of this ranking and the absolute VAMP-2 scores for lag time~$0.5$~ns in Fig.~\ref{fig:io-to-tica}b.
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We find that backbone torsions contain more kinetic variance than the backbone heavy atom positions or the distances between them (Fig.~\ref{fig:io-to-tica}b).
@@ -584,7 +584,7 @@ \subsection{Modeling large systems}
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This problem may be mitigated by choosing a more specific set of features.
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Additional technical challenges for large systems include high demands on memory and computation time;
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we explain how to deal with those in the tutorials (Notebook 00 and 02).
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we explain how to deal with those in the tutorials (notebooks~00 and~01).
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More details on how to model complex systems with the techniques presented here are described, e.g., by~\cite{plattner_protein_2015,plattner_complete_2017}.
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