Number of different structural and sequential clusters derived from CATH database.

<p>Blue dots represent proteins with less than 5 BPs and the orange ones those with 5 or more BPs. It is possible to see that proteins with more than 5 BPs are more diverse structurally and sequentially.</p

Structure of dethiobiotin synthase (PDB ID 1byi) represented in cartoon representation showing mapped BPs.

<p>Red indicates ACE inhibitor BP activity (14), blue antibacterial (4), yellow inmunomodulating (3), green antioxidative (3), magenta neuropeptide (1), light grey chemotactic (1) and dark grey stimulating activities (1) (as derived from BIOPEP database). It is possible to see that different activities have similar location. BPs found in different proteins of the same superfamily have been mapped on a representative structure (1byi) accordingly to CATH (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191063#sec002" target="_blank">Materials and methods</a>).</p

Flowchart of main procedure followed to mapping the structural occurrence of biopeptides.

<p>Flowchart of main procedure followed to mapping the structural occurrence of biopeptides.</p

Description of the top ten most abundant superfamilies found in the assignation of structure of the sequences with at least one peptide.

<p>Description of the top ten most abundant superfamilies found in the assignation of structure of the sequences with at least one peptide.</p

Distribution of number of GO terms associated with folds with more and less than 5 biopeptides.

<p>Distributions of different GO terms per each class (Molecular function, Cellular components and Biological process) for proteins showing less than 5 and 5 or more BP (panels a, b, and c). Panel d, shows the same distribution but now using FunTree clusters information. In all the cases it is possible to observe that proteins with more than 5 BPs are functionally more diverse than those proteins with less than 5 BPs.</p

Detail of the sequence and activity of biopeptides of the first four superfamilies with the highest number of biopeptides.

<p>The activity corresponds to the classification in BIOPEP.</p

Diagram of structural mapping of the bioactive peptides on structural superfamilies.

<p>Once a BP was detected in a given protein after sequence exact searches, we identified putative folds for that sequence using fold-assignment techniques. Templates in this fold identification were those domains deposited in CATH database. We then structurally aligned the sequence putative CATH template with the corresponding representative protein of the structural superfamily again accordingly with CATH database. We finally mapped the BP occurrence to the representative template of each structural superfamily.</p

Addressing the Role of Conformational Diversity in Protein Structure Prediction

<div><p>Computational modeling of tertiary structures has become of standard use to study proteins that lack experimental characterization. Unfortunately, 3D structure prediction methods and model quality assessment programs often overlook that an ensemble of conformers in equilibrium populates the native state of proteins. In this work we collected sets of publicly available protein models and the corresponding target structures experimentally solved and studied how they describe the conformational diversity of the protein. For each protein, we assessed the quality of the models against known conformers by several standard measures and identified those models ranked best. We found that model rankings are defined by both the selected target conformer and the similarity measure used. 70% of the proteins in our datasets show that different models are structurally closest to different conformers of the same protein target. We observed that model building protocols such as template-based or <i>ab initio</i> approaches describe in similar ways the conformational diversity of the protein, although for template-based methods this description may depend on the sequence similarity between target and template sequences. Taken together, our results support the idea that protein structure modeling could help to identify members of the native ensemble, highlight the importance of considering conformational diversity in protein 3D quality evaluations and endorse the study of the variability of the native structure for a meaningful biological analysis.</p></div

Structure of TTR-T4 complex.

<p>T4 molecules are displayed in the binding cavities as spheres and TTR monomers as ribbons. (a) The two monomers present in the asymmetric unit of the crystal structures used are labelled as A and B, symmetry related monomers as A’ and B’. (b) View of the A-A’ monomer-monomer interface.</p

Values of for different ligands.

<p>Values of for different ligands.</p