The meta-structure was introduced C646 concentration as a novel concept for protein sequence analysis [34]. In this approach a protein is conceived as a network in which individual amino acids represent the nodes whereas edges connecting two nodes indicate spatial proximity in the 3D structure. Of particular relevance is the fact that in this conceptual view the mutual couplings between individual amino acids and the resulting cooperative character of the protein are retained. It has been shown that the network structure of a protein can be calculated exclusively

based on primary sequence information and statistical distribution functions derived from the PDB database [34]. The meta-structure of the protein is quantified by two sequence-derived parameters, compactness and local secondary structure. Residue-specific compactness values quantify the spatial embedding

of individual residues within the 3D protein structures. Residues in the interior of a structure learn more exhibit large compactness values while residues located on the surface and exposed to the solvent display small (even negative in case of conformationally highly flexible segments) values. The meta-structure derived secondary structure parameter is defined in analogy to the well-established NMR 13Cα chemical shift index, with positive values for α-helices and negative values indicating the presence of an extended conformation. It has already been shown that this novel approach is very useful for the analysis of IDPs [34] and [35]. Firstly, a large scale comparison of calculated compactness values of IDPs (taken from the DisProt database) with well-folded proteins deposited in the PDB database showed that IDPs display significantly smaller compactness values (∼230) compared to their well-folded counter parts (∼330) suggesting Meloxicam that compactness

values are valuable quantitative probes for structural compaction of proteins [34]. Additionally, it was demonstrated that calculated local secondary structure parameters are indicative of α-helices and β-strands [36]. Consistently positive values are found for residues located in α-helical segments while residues populating extended structural elements (β-strands or polyproline II helices) display negative values. A comparison of meta-structure and NMR data for a prototypical IDP is given in Fig. 3. It can be seen that meta-structure values convincingly compare with experimental NMR secondary chemical shifts or NMR-derived secondary structure propensities. Novel applications to large-scale, sequence-based protein analysis and selection (e.g. identification of IDPs displaying significant local α-helical preformation) are feasible and have already been suggested [36]. Here another application of meta-structure data (e.g. compactness) is proposed.