The PentUnFOLD algorithm as a tool to distinguish the dark and the light sides of the structural instability of proteins

Abstract

Intrinsically disordered proteins are frequently involved in important regulatory processes in the cell thanks to their ability to bind several different targets performing sometimes even opposite functions. The PentUnFOLD algorithm is a physicochemical method that is based on new propensity scales for disordered, nonstable and stable elements of secondary structure and on the counting of stabilizing and destabilizing intraprotein contacts. Unlike other methods, it works with a PDB file, and it can determine not only those fragments of alpha helices, beta strands, and random coils that can turn into disordered state (the “dark” side of the disorder), but also nonstable regions of alpha helices and beta strands which are able to turn into random coils (the “light” side), and vice versa (H ↔ C, E ↔ C). The scales have been obtained from structural data on disordered regions from the middle parts of amino acid sequences only, and not on their expectedly disordered N- and C-termini. Among other tendencies we have found that regions of both alpha helices and beta strands that can turn into the disordered state are relatively enriched in residues of Ala, Met, Asp, and Lys, while regions of both alpha helices and beta strands that can turn into random coil are relatively enriched in hydrophilic residues, and Cys, Pro, and Gly. Moreover, PentUnFOLD has the option to determine the effect of secondary structure transitions on the stability of a given region of a protein. The PentUnFOLD algorithm is freely available at http://3.17.12.213/pent-un-fold and http://chemres.bsmu.by/PentUnFOLD.htm . Supplementary Information The online version contains supplementary material available at 10.1007/s00726-022-03153-5.

Peptide Models of the Cytoplasmic Tail of Influenza A/H1N1 Virus Hemagglutinin Expand Understanding its pH-Dependent Modes of Interaction with Matrix Protein M1

“…We further addressed the in silico structural stability of the HA CT region based on the analysis of its amino acid sequence. For this, we applied a recently developed PentUnFOLD algorithm [ 23 ] that exists as three versions (1D, 2D, and 3D) to a model peptide FI15 (Table 1 ). At pH 7.4, a beta hairpin consisting of two beta strands (Trp2-Met3 and Gln10-Cys11) is determined by the DSSP and also by the 2D version of PentUnFOLD algorithm [ 23 ].…”

“…For this, we applied a recently developed PentUnFOLD algorithm [ 23 ] that exists as three versions (1D, 2D, and 3D) to a model peptide FI15 (Table 1 ). At pH 7.4, a beta hairpin consisting of two beta strands (Trp2-Met3 and Gln10-Cys11) is determined by the DSSP and also by the 2D version of PentUnFOLD algorithm [ 23 ]. The first beta strand is more stable since Met3 is defined as stable beta strand residue (“ES” according to [ 23 ]) (Table 1 ).…”

“…At pH 7.4, a beta hairpin consisting of two beta strands (Trp2-Met3 and Gln10-Cys11) is determined by the DSSP and also by the 2D version of PentUnFOLD algorithm [ 23 ]. The first beta strand is more stable since Met3 is defined as stable beta strand residue (“ES” according to [ 23 ]) (Table 1 ). At the same time, the second beta strand is defined as nonstable (“EN”).…”

“…* *1D, 2D and 3D are three different versions of the PentUnFOLD algorithm [ 23 ]. «CE» is a fragment of random coil capable to structural transition to beta strand; «CH» is a fragment of random coil capable to structural transition to alpha helix; «ES» are residues of beta strands that have a low probability to turn into random coil; «EN» are residues of beta strands that have a high probability to turn into random coil; «D» is a disordered state; «O» is an ordered state [ 23 ]. The boundaries of beta strands defined by each version of the PentUnFOLD algorithm are highlighted in yellow …”

“…Stability of the secondary structure of the HA CT region and its ability to undergo structural transitions was evaluated by the PentUnFOLD web server using all versions of that algorithm [ 23 ].…”