+\section{Protein Disorder Prediction}
+\label{protdisorderpred}
+
+Disordered regions in proteins were classically thought to correspond to
+'linkers' between distinct protein domains, but disorder can also play a role in
+function. The {\sl Web Services $\Rightarrow$ Disorder} menu in the alignment window
+allows access to protein disorder prediction services provided by the configured
+JABAWS servers.
+
+\subsection{Disorder prediction results}
+Each service operates on sequences in the alignment to identify regions likely
+to be unstructured or flexible, or alternately, fold to form globular domains.
+As a consequence, disorder predictor results include both sequence features and
+sequence associated alignment annotation rows. Section \ref{featannot} describes
+the manipulation and display of these data in detail, and {\bf Figure
+\ref{alignmentdisorder}} demonstrates how sequence feature shading and
+thresholding (described in Section \ref{featureschemes}) can be used to
+highlight differences in disorder prediction across aligned sequences.
+
+\begin{figure}[htbp]
+\begin{center}
+\includegraphics[width=5in]{images/disorderpred.pdf}
+\caption{{\bf Shading alignment by sequence disorder}. Alignment of Interleukin IV homologs coloured with Blosum62 with protein disorder prediction sequence features overlaid, shaded according to their score. Borderline disordered regions appear white, reliable predictions are either Green or Brown depending on the type of disorder prediction. }
+\label{alignmentdisorder}
+\end{center}
+\end{figure}
+
+\subsubsection{Navigating large sets of disorder predictions}
+
+{\bf Figure \ref{alignmentdisorderannot}} shows a single sequence annotated with
+a range of disorder predictions. Disorder prediction annotation rows are
+associated with a sequence in the same way as secondary structure prediction
+results. When browsing an alignment containing large numbers of disorder
+prediction annotation rows, clicking on the annotation row label will highlight
+the associated sequence in the alignment display, and double clicking will
+select that sequence.
+
+\begin{figure}[htbp]
+\begin{center}
+\includegraphics[width=5in]{images/disorderpredannot.pdf}
+\caption{{\bf Annotation rows for several disorder predictions on a sequence}. A zoomed out view of a prediction for a single sequence. The sequence is shaded to highlight disorderd regions (brown and grey), and the line plots below the Sequence show the raw scores for various disorder predictors. Horizontal lines on each graph mark the level at which disorder predictions become significant. }
+\label{alignmentdisorderannot}
+\end{center}
+\end{figure}
+
+
+\subsection{Disorder predictors provided by JABAWS 2.0}
+For full details of each predictor and the results that Jalview can display,
+please consult
+\href{http://www.jalview.org/help/html/webServices/proteinDisorder.html}{Jalview's
+protein disorder service documentation}. Short descriptions of the methods provided in JABAWS 2.0 are given below:
+
+\subsubsection{DisEMBL}
+\href{http://dis.embl.de/}{DisEMBL (Linding et al., 2003)} is a set of machine-learning based predictors trained to
+recognise disorder-related annotation found on PDB structures.
+
+\textbf{COILS} Predicts
+loops/coils according to DSSP
+definitions\footnote{DSSP Classifications of secondary structure are: $\alpha$-helix (H), 310-helix (G), $\beta$-strand (E)
+are ordered, and all other states ($\beta$-bridge (B), $\beta$-turn (T), bend (S),
+$\pi$-helix (I), and coil (C)) considered loops or coils.}. Features mark range(s) of
+residues predicted as loops/coils, and annotation row gives raw value
+for each residue. Value over 0.516 indicates loop/coil.
+
+\textbf{HOTLOOPS} constitute a refined subset of \textbf{COILS}, namely those loops with
+a high degree of mobility as determined from C$\alpha$ temperature factors (B
+factors). It follows that highly dynamic loops should be considered
+protein disorder. Features mark range(s) of residues predicted to
+be hot loops and annotation row gives raw value for each
+residue. Values over 0.6 indicates hot loop.
+
+\textbf{REMARK465} ``Missing
+coordinates in X-ray structure as defined by remark465 entries in PDB.
+Nonassigned electron densities most often reflect intrinsic disorder,
+and have been used early on in disorder prediction.'' Features give
+range(s) of residues predicted as disordered, and annotation rows gives
+raw value for each residue. Values over 0.1204 indicates disorder.
+
+\subsubsection{RONN {\sl a.k.a.} Regional Order Neural Network}
+\href{http://www.strubi.ox.ac.uk/RONN}{RONN} employs an approach
+known as the `bio-basis' method to predict regions of disorder in
+sequences based on their local similarity with a gold-standard set of
+disordered protein sequences. It yields a set of disorder prediction
+scores, which are shown as sequence annotation below the alignment.
+
+\textbf{JRonn}\footnote{JRonn denotes the score for this server because JABAWS
+runs a Java port of RONN developed by Peter Troshin and distributed as
+part of \href{http://www.biojava.org/}{Biojava 3}} Annotation Row gives RONN score for each residue in
+the sequence. Scores above 0.5 identify regions of the protein likely
+to be disordered.
+
+\subsubsection{IUPred}
+\href{http://iupred.enzim.hu/Help.php}{IUPred} employs
+an empirical model to estimate likely regions of disorder. There are
+three different prediction types offered, each using different
+parameters optimized for slightly different applications. It provides
+raw scores based on two models for predicting regions of `long
+disorder' and `short disorder'. A third predictor identifies regions
+likely to form structured domains.
+
+\textbf{Long disorder} Annotation rows predict
+context-independent global disorder that encompasses at least 30
+consecutive residues of predicted disorder. A 100 residue
+window is used for calculation. Values above 0.5 indicates the residue is
+intrinsically disordered.
+
+\textbf{Short disorder} Annotation rows predict for short, (and
+probably) context-dependent, disordered regions, such as missing
+residues in the X-ray structure of an otherwise globular protein.
+Employs a 25 residue window for calculation, and includes adjustment
+parameter for chain termini which favors disorder prediction at the
+ends. Values above 0.5 indicate short-range disorder.
+
+\textbf{Structured domains} are marked with sequence Features. These highlight
+likely globular domains useful for structure genomics investigation. Post-analysis of disordered region profile to find continuous regions
+confidently predicted to be ordered. Neighbouring regions close to
+each other are merged, while regions shorter than the minimal domain
+size of at least 30 residues are ignored.
+
+\subsubsection{GLOBPLOT}
+\href{http://globplot.embl.de/}{GLOBPLOT} defines regions of
+globularity or natively unstructured regions based on a running sum of
+the propensity of residues to be structured or unstructured. The
+propensity is calculated based on the probability of each amino acid
+being observed within well defined regions of secondary structure or
+within regions of random coil. The initial signal is smoothed with a
+Savitzky-Golay filter, and its first order derivative
+computed. Residues for which the first order derivative is positive
+are designated as natively unstructured, whereas those with negative
+values are structured.
+
+{\bf Disordered region} sequence features are created marking mark range(s) of residues with positive first order derivatives, and
+\textbf{Globular Domain} features mark long stretches of order. \textbf{Dydx} annotation rows gives the first order derivative of smoothed score. Values above 0 indicates
+residue is disordered.
+
+\textbf{Smoothed Score and Raw Score} annotation rows give the smoothed and raw scores used to create the differential signal that
+indicates the presence of unstructured regions. These are hidden
+by default, but can be shown by right-clicking on the alignment
+annotation panel and selecting \textbf{Show hidden annotation}.