HCAtk and pyHCA: A Toolkit and Python API for the Hydrophobic Cluster Analysis of Protein Sequences

Tristan Bitard-Feildel; Isabelle Callebaut

HCA score 104 The HCA score, used to compute a p-value associated with each HCA domain, is defined as follow. Each 105 residue of an HCA segment is associated with a class regarding the residue type and hydrophobicity. Such 106 a residue is either in an hydrophobic cluster and hydrophobic, in an hydrophobic cluster and hydrophilic, 107 or outside an hydrophobic cluster. A value is attributed to each class and the HCA score is computed as Figure S3 : Disordered regions with low HCA score -example n o 1. The HCA pattern displayed by the disordered region is typical of non globular regions, with very few clusters and many proline (star symbols). The disordered region corresponds to the sequence segment from amino acids 85 to 198 of the human Cyclin-dependent kinase inhibitor p27(Kip1) (Uniprot P46527). Figure S3 corresponds to the C-terminal sequence of the human Cyclin-dependent kinase inhibitor p27. 134 p27Kip1 controls eukaryotic cell division through interactions with cyclin-dependent kinases [22] and is 135 known as a flexible protein [13] , whose stability is associated with phosphorylation. The C-terminal region 136 of p27 has a high flexibility, which provides the molecular basis for the sequential signal transduction 137 conduit that regulates its own degradation and cell division [3, 13] ). The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/249995 doi: bioRxiv preprint has a DNA binding motif [23] , whose activity requires a high level of intrinsic flexibility. Examples of disordered regions with high HCA scores. the TGF-beta receptor [7, 28] . The HCA pattern displayed by the disordered region is similar to patterns 156 observed for foldable regions, suggesting that this small domain is able to fold, at least under particular Figure S5 : Disordered regions with high HCA score -example n o 1. The HCA pattern displayed by this disordered region is similar to patterns observed for foldable regions. Clusters of hydrophobic residues, whose length are typical of stable regular secondary structures, are separated by regions whose lengths are typical of loops. This disordered region corresponds to an internal segment, from amino acids 291 to 352, of the chicken's zinc finger FYVE domain-containing protein 9 (UniProt O95405), without known function.