| Analysis of fuzzy complexes FuzDB can be used to interpret experimental data of a system of interest or to perform comparative analysis. i) To decide whether your complex is fuzzy. • Enter your technique in the “Detection method” of the advanced search option of the Search module. Fuzzy complexes, which were determined by the same method will be listed. • If structural data has been deposited, it is displayed under PDB (Protein Data Bank) or BMRB (Biological Magnetic Resonance Bank). By simply clicking the corresponding identifiers, you will be directed to these structural databases. • If structural data has not been deposited, or you seek for interpretation of data indicating fuzziness. By clicking either the FCxxxx identifier of the complex, or the protein name, you can open the Expanded Entry page of a complex. In the “Structural evidence” section the structural data, which indicate dynamic disorder or polymorphism in the bound state will be detailed. • In the “Structure/Mechanism” section of the Expanded Entry page, you may find different scenarios on the molecular mechanisms how fuzziness affects function of the complex. ii) Functional analysis of fuzzy complexes. • Fuzzy complexes with given functions (e.g. transcription) could be selected in the simple text search of the Search module. • By clicking either the FCxxxx identifier of the complex, or the protein name, you can open the Expanded Entry page of a complex. “Biological function” describes the biological roles of the fuzzy complex and “Biochemical evidence” specifies the contribution of the fuzzy region, for which structural evidence has been provided. • In vitro or in vivo “Biochemical evidence” is derived from binding or kinetic data, transcriptional or aggregation assays etc. obtained on variants, where the fuzzy region is affected by site-directed mutagenesis, truncation or deletion experiments. iii) Regulatory features of fuzzy complexes. • An overview of regulatory features of the fuzzy region is given in the post-translational modifications and the isoforms, context-dependence sections of the Expanded Entry page. Context-dependence refers to environment-dependent functional features of the different isoform, which are modulated by the PTM or AS of the fuzzy region. This information can complement and be combined with the molecular mechanism which is described in the Expanded Entry page, and can help to interpret the structural and functional properties of the system of interest under different conditions. Comparative analysis A comparative analysis can be performed via the advanced option of the Search module using data either in the Table of Entries or in the Expanded Entry page, such as organism, partner, function, topology or mechanism. Individual as well as combined categories can be used. Comparative analysis I. • Fuzzy complexes from a specific organism could be selected via the advanced search option of the Search module. • Propensities of different fuzzy complex topologies specified in the “Class” column of the table could be computed and compared between different organisms. • A histogram of the lengths of fuzzy regions could be computed and compared between different organisms. Comparative analysis II. • One may use a combination of “detection method” and “topology” in the advanced search option of the Search module. This will inform about what kind of fuzzy complexes could be determined/characterized by a given technique. For example, random fuzzy complexes are rarely observed by X-ray, but NMR is highly useful to detect them. • One may use a combination of “detection method” and “mechanism” in the advanced search option of the Search module. This provides information on the techniques, which are suitable to characterize different mechanisms. Comparative analysis III. • Fuzzy complexes conforming to a given topology (polymorphic, clamp, flanking, random) could be selected using advanced search option of the Search module. The propensities of the different topology categories could be derived. • Use an additional filter for the mechanism: conformational selection, entropy or flexibility modulation, competitive binding or tethering. • Such a combination of topology and mechanism categories highlights the preferred molecular scenarios for a given type of fuzzy complex, e.g. flanking fuzzy regions often compete with the structured binding sites. For more details of the mechanism, please visit the Expanded Entry page by clicking either the FCxxxx identifier of the complex, or the protein name.
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