Chameleon Sequences: Ordered or Disordered

doi:10.21203/rs.3.rs-2750547/v1

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Chameleon Sequences: Ordered or Disordered

https://doi.org/10.21203/rs.3.rs-2750547/v1

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Chameleon seqeuences represent a class of sequences violating the important paradigm of molecular biology of one sequence-one structure. Chameleon sequences adopt two different structures in the same protein or in another protein. Why these short sequences are capable of changing their structure has remained unknown. We have examined some properties of chameleon sequences and compared them with those from intreinsically disordered regions of proteins and sequences with known unique secondary structure. Our results show that chameleon sequences have charge distributions very similar to ordered sequences. The GRAVY value of ordered sequences differ from that of intrinsically disordered sequences. Chameleon sequences have GRAVY values close to ordered sequences. A charge-hydropathy plot cleary demonstrated the distribution of ordered, chameleon, and intrinsically disordered regions of proteins. Here again, chameleon sequences placed themselves close to ordered sequences. A conformational analysis of chameleon sequences revealed slight deviations of dihedral angles from ordered sequence values. Based on our analysis we propose that chameleon sequences, with close distance to ordered sequences, have gained limited capability of changing their secondary structure under suitable conditions.

Biological sciences/Structural biology

Biological sciences/Biophysics

Biological sciences/Biophysics/Computational biophysics

Biological sciences/Biophysics/Intrinsically disordered proteins

Biological sciences/Biophysics/Molecular biophysics

Proteins adopt a unique steric fold mostly governed by their sequence of amino acids. The paradigm that a given sequence always ends up with a unique fold has been challenged by several instances. Chameleon sequences represent one of the instances of a given sequence with more than one secondary structure. First discovered by Kabsch and Sander¹, Kim and Minor² coined the name chameleon for these sequences. Chameleon sequences have similar tendency to form helical, beta, or coil structures ³.chameleon sequences include three categories of secondary structure transitions; helix to coil transition (HC), sheet to coil transition (EC), and helix to sheet transitions (HE) and vice versa. Chameleon sequences are responsible for many important functions of proteins, such as conserved protein folding and functional diversity in multiple splicing protein isoforms⁴, detection phenomena in immune system ⁵ and formation of many disease such as amyloid fibril diseases^6,7, and are important parameters in solving folding problems (sequence to structure relation). Chameleon sequences produce error in secondary structure prediction methods⁸ Therefore, identification and characterization of these sequence is necessary for the correct modeling and prediction of protein secondary structure ⁹. Structural transitions in chameleon sequences can either occur in homologous proteins or in non-homologous proteins. In the first case a given sequence in a protein may undergo various transitions under various environmental or physiological conditions. It is said pH changes, mutation and conformational contagion or neighboring sequence conformation induces different conformations in chameleon sequences. Why these sequences change their structure is not fully understood.

Sidechain hydrophobicity constitute the major factor in the correct folding of proteins. Residues with hydrophobic sidechains are usually completely folded and buried. Therefore, proteins with high number of hydrophobic residues are well-ordered proteins with very little structural flexibly¹⁰. On the other hand, residues with non-hydrophobic sidechains place themselves on the surface of proteins and constitute major building blocks of the flexible parts of proteins ¹¹. Charged residues can also be an important factor in protein folding and unfolding. The amount of the charge and their distribution pattern play an important role in forming flexible structures ^12,13. The balance between hydrophobicity and non-hydrophobicity, e.g., the charge of residues, has been used as an indicator for classification of ordered versus flexible or disordered proteins. Uveresky employed a charge-hydropathy plot for classification of proteins. In this plot, the absolute mean net charge was plotted against the mean hydropathy. It divided the space into two distinct zones, the order and disorder proteins were located in two distinct areas¹⁴. The plot has relatively high accuracy, separating 95% of order proteins and 75% of the disorder proteins. Therefore, these plot became a useful tool for IDP/IDR prediction ¹⁵. Conformational state of a protein largely reflects spatial stability of the protein^16,17. The known loci of stable secondary structures almost entirely coincide with area of minimal conformationl energy of the protein ¹⁸. Therefore, an analysis of the conformationa state of a peptide indicates the extent of the stabity of that peptide.

Here, to understand why chameleon sequences adopt different structures under various conditons we have analysed the charge and hydropathy pattern of chameleon sequences along with the conformational state of these sequences and compared it with normal stable sequences of similar secondary structures and size and with sequences of similar length from intrinsically disordered protein. Our result indicated close proximity of chameleon sequences to ordered structures rather than intrinsically disordered sequences. Slight deviations from parameters of ordered sequences allow chameleon sequences to adopt alternative structures under suitable conditions.

2.1-Databases

We used PISCES (http://dunbrack.fccc.edu/PISCES.php) to select PDB protein entries with minimum of 40 amino acids in length whose structures has been determined by X-ray crystallography with maximum resolution of 2.5 Å and maximum R value of 0.3 .

2.2-Chameleon sequence determination

We used in house program ¹⁹ to identify and retrieve chameleon sequences in homologus proteins based on DSSP assignment of secondary structures (https://swift.cmbi.umcn.nl/gv/dssp/). The 8 classes of secondary structures in DSSP (G, H, I, T, E, B, S,) were combined and reduced to 3 classes. Accordingly, G, H, and I were classified as helices (H). The T, S, B and C were classified as coils (C). The E, and B were classified as sheets (E).

2.3- Disordered sequence determination

We used disordered protein database Disprot (https://www.disprot.org/ ) to select all pieces of disordered proteins with length between 5–12 residues. 936 disordered sequences were selected. Disprot is a database that collects experimental data in this field and the data is not selected as a predictor in this work ²⁰.

2.4- Ordered Sequences

We selected sequences with 5–12 residues from PDB entries not included in Chameleon sequences and not included in Disprot.

2.5-Absolute charge per residue (ACPR) calculation

The peptide charge was calculated at the EXPASY site. Absolute charge per residue or fraction of charge residues (ACPR) was determined by calculating the sum of fraction of positive and negative charges in each sequence. Probability Density diagrams were used to show the distribution of data in three groups of sequences under study. A density plot is a graph that shows the distribution of a numerical variable. It is actually a smoothed version of the histogram. Uses kernel density estimates to represent the variable probability density function. The probability distribution function expresses the rate of events occurrence .

2.6- GRAVY calculation

GRAVY (GRand AVerage of hydropathicitY index) is used to determine the amount of hydrophilicity and hydrophobicity. The hydropathy value obtained was divided to the number of residues in each sequence.

The hydropathy for all kind of sequences was calculated using the Kyte and Doolittel method ²¹ on the EXPASY site by ProtParam (https://web.expasy.org/cgi-bin/protparam/protparam).

We used adensity diagram to visualize the data obtained for studied sequences, because this type of plot can convey information about the frequency and distribution of data as described above.

2.7- Charge-Hydropathy Graphs

For all of chameleon groups, ordered, and disordered sequence the net charge per residue and hydropathy per residue for each group was calculated and plotted.

2.8- Ramachandran plots

Phi and Psi values of residues from chameleon and ordered sequences were derived from relevant DSSP files (http://swift.cmbi.ru.nl/gv/dssp/).

Mean values for phi and psi angles were calculated using circular average method ²². Due to periodic nature of dihedral angles a simple averaging is not suitable and may provide false results. The average value for a dihedral angle from a sequence is given by the formula:

A_ave=Arctan(∑sinA_i/∑cosA_i)

In which A represent a dihedral angle.

To compare the conformational state of chameleon sequences with ordered and disordered sequences of similar sizes first we calculated for every sequence an average value for each of dihedral angles phi and psi and plotted them on a phi-psi diagram. Next, these average values were further averaged over all sequences of a given type to give a sinlge value for phi and psi for that type of sequence. The result was plotted on the phi-psi diagram. In order to be able to compare the obtained plots we calculated the distance between the points using the Euclidean distance calculation method. The Euclidean distances between these points reflect the conformational distances between various types of sequences.

3.1-Dataset

We obtained 287656 entries that were used for identification of chameleon sequences. All sequences were matched for the number of residues between 5 to 12 residues.

3.2- Absolute charge per residue

Three groups of sequences were selected; chameleon sequences, ordered sequences, and intrinsically disordered sequences. Chameleon sequences included coil- sheet transition(CE), helix-coil transition(HC), helix-sheet transition(HE), and vice versa.

Positive and negative charges of each sequence was calculated using the data of EXPASY web server tool (https://www.expasy.org), then sum of fraction of positive and negative charge values were calculated for each sequence and called ACPR (absolute charge per residue).

As shown in Fig. 1A the ACPR average for chamseqs, IDRs and ORDs were 0.26, 0.3 and 0.26 respectively, which shows that chameleon sequences very closely behaves like ordered sequences. Figure 1B shows the ACPR distribution in three groups of chameleon sequences, ordered and intrinsically disordered sequences. The x-axis in density plot shows the range of values in the data set and the y-axis shows the probability density function for the kernel density estimation mean the probability per unit on the x-axis. The peak in this chart is where we have the most data concentration. If there are several peaks, the chart is multi-modal. ACPR in chamseq and ORDs are multimodal with four peak points in 0.0, 0.2 ,0.4, 0.6 and 0.8. The data frequency in 0.2 is highest. In some points there are not any data. The graph is sharper in Chameleon sequences than in ordered sequences. The density plot for IDRs has one peak. The highest data density is at point 0.2. It is true that small peaks are seen in points 0.4, 0.6 and 0.8, with the difference that the graph is integrated, which means that we continuously observe the possibility of data presence in all points and shows a relatively uniform ACPR distribution.

3–3. Hydropathy

We used hydropathy per residue values to compare chameleon sequences with intrinsically disordered and ordered sequences. We employed Kyte-Doolittle scale as described above and calculated GRAVY (sum of hydropathy values of all amino acids divided by the sequences length²¹), as described in section 2.7, for all group of sequences under study. The average of GRAVY in three groups are − 0.1 for IDRs ,-0.16 for ORDs, and 0.1 for chameleon sequences (Fig. 2A). We used a density plot to examine the distribution of data (Fig. 2B). ORDs and IDRs have unimodal distribution; meaning they have one peak in the plot. Peaks indicate more data repetition. Statistically, they are actually the same mode or frequency. Chamseqs are multimodal and have three peaks. Peaks in ORDs and Chamseqs have almost normal distribution. The GRAVY values in chamseq is between − 4.3 and 4.2, and the highest frequency is around 0.5 and − 0.5 respectively. The GRAVY values in ORD sequences is between − 4.1 and 3.2, and the highest frequency is around − 0.1. In IDRs, GRAVY is between − 4 and 3.2 and the highest frequency is in -1.5 value. In other words, chameleon sequences are more hydrophobic and ordered and disordered sequences are more hydrophilic.

3–4. charge – hydropathy plot

To compare the distribution of chameleon sequences with ordered and disordered sequences on the charge- hydropathy space (C-H plot) we calculated the distribution center of the points using the data mean. We calculated the mean of C-H values of all sequences in each group on this graph. The result is shown in the Fig. 3. Ordered and disordered sequences are well separated, while chameleon sequences lie close to ordered sequences.

3–5. Ramachandron plot

The distribution of backbone dihedral angles for each residue and sequences in chameleon sequences undergoing helix-coil(HC), helix- sheet(HE), sheet-coil(EC), and vise versa transition were investigated.

Figure 4 shows the Ramachandran plot for each amino acid in 3 types of chameleon sequences (CE,HE,CH). In Fig. 4A the phi and psi values for residues undergoing sheet-coil transitions (CE) is shown. Dihedral torsion angles of sheets undergoing coil transitions occupy a broader range in the Ramachandran plot. According to the Klarplus division the phi and psi angles cover alpha helices and beta region, polypeptide II erea (P_II), P_II′, γ, γ′, ζ, δ, δ′ regions .The points in the corners of the plot corresponding to the ε regions where glycines are located²³. Dihedral torsion angles of coils undergoing sheet transitions covers almost the same areas, with the difference that the density of points in the beta and P_II region has decreased and in other sections increased. The points in the three corners of the plot are more scattered.

Figure 4B shows the distribution of dihedral angles of chameleon sequences undergoing helix-sheet transition. Both helical and beta regions are well separated. Helical structures of chameleon sequences occupy the allowed region of α and δ regions in the Ramachandran plot according to the karplus division²³. Chameleon sequences with sheet structure occupy the left upper corner of the Ramachandran plot where it belongs to the beta and polypeptide II and ζ and γ′ regions. Scattered points are also seen in the δ′ region.

Figure 4C shows the distribution of dihedral angles of chameleon sequences undergoing helix-coil transition. Helical structures of chameleon sequences occupy the allowed region of region of α and δ regions in the Ramachandran plot. Most of the data related to the studied coil structures are outside the allowed region in the classic Ramachandran diagram. Of course, they are mostly around the allowed region and most angles outside of these areas are related to glycine.

Figure 5 shows the Ramachandran plot for each Chameleon sequences in 3 types of chameleon sequences (CE, HE, CH). The phi and psi values of the residues participating in a chameleon sequence are averaged and one phi and psi value is assigned to each sequence. Since phi and psi angles are part of directional data and these data do not have a definite zero, so calculating the average in this data in the usual way creates an error in the results. Therefore, a type of statistics called circular statistics or directional statistics was used. To calculate the average phi and psi angles through circular statistics, first the calculated angles was pointed on a circle with unit radius, then these polar coordinates was converted to Cartesian coordinates and these Cartesian coordinates were averaged using the usual average method.

In Fig. 5A the average of phi and psi values for sequences undergoing sheet-coil transitions is shown. The average phi and psi values of sheet structure are located in beta region. Figure 5B shows the distribution of average values of dihedral angles of chameleon sequences undergoing helix-sheet transition or vise versa. Both helical segment and sheet segments are well separated. Almost all the points are located in the alpha and beta region.

Figure 5C shows the distribution of average dihedral angles of chameleon sequences undergoing helix-coil transition. Helical structures of chameleon sequences occupy the allowed region of helix structure in the Ramachandran plot. Chameleon sequences with coil structure scattered in the left half of the chart.

In Fig. 6, the centers of dihedral angle distribution in chameleonic helix and sheet sequences and two groups of normal sequences(alpha-helix and beta sheet) and coil have been drawn.

The Euclidean distance between the points corresponding to the normal sheet and chameleonic sheet sequences and normal helix and chameleonic helix sequences are calculated and are presented in Table 1. The distribution centers of the dihedral angles of Chameleonic helix are slightly different from the distribution centers of the normal helix dihedral angles. This distance is equal to 8 degrees. The distribution center of chameleonic beta sheet dihedral angles have been deviated by 13.6 degree from the centers of distribution of dihedral angles of normal beta sheets.

Table 1

The Euclidean distance between the points corresponding to the sheet and helix chameleon sequences and normal sequences
Group	Distance
H-Chamseq & H-ORD	8^o
E-Chamseq & E-ORD	13.6^o

Chameleon sequences are short sequences that adopt various secondary structures under different conditions. How and by what mechanism these sequences change their structure has not been clarified. These sequences create problems in predicting the secondary structure. On the other hand, solving the mechanism of their structure change brings us closer to solving the problem of protein folding. Also, these sequences can be the beginning of partial changes in protein folding and they can make the protein to lead to aggregation/fibrillation. These reasons make studying these sequences important.

In this study, chameleon sequences have been investigated from the perspective of physicochemical characteristics such as hydropathy, charge, CH plots and structural characteristics such as the study of dihedral angles (Phi and Psi angls). Then these features were compared with ordered and disordered sequences.

The results show that chameleon sequences behave similar to ordered sequences in terms of charge and hydropathy. The hydropathy values in chameleon and ordered sequences show that these sequences are almost neutral sequences in terms of hydrophobicity.

From the point of view of structural features, chameleon sequences that have a helix or sheet structure are placed in the Ramachandran diagram with a slight deviations from the helix and sheet regions.

Physicochemical characteristics such as charge and hydropathy are very important in understanding protein structure and flexible regions. It has been shown that charged and/or hydrophilic residues have a greater contribution to the flexible regions. Uveresky created a two-dimensional predictor from the combination of average charge and average hydropathy features that separated intrinsically disordered and ordered proteins. In this work, high charge and low hydropathy will create flexibility ¹⁴. In another work, the distribution and pattern of charge was investigated. Intrinsically disordered proteins have opposite charges within a sequence and their net charge is almost neutral, these sequences have a high charge, and about 75 percent of them have a charge fraction above 0.35 ²⁴. It has been shown that hydrophobicity and surface charge play a role in the formation of aggregation in IgG antibodies²⁵. The combination of these two features, i.e. charge and hydropathy, can be a simple and somewhat reliable tool to identify the flexibility or rigidity of protein structure ²⁶. We used charge and hydrophobicity to compare chameleon sequences with ordered and intrinsically disordered sequences of similar sizes.

In Fig. 1, the average value and the distribution of ACPR for the 3 sub-groups of Chamseq, ORDs, and IDRs is shown. This diagram is multimodal, i.e. three peak are observed at points 0.2, 0.4, 0.6, and a very small peak at 0.8. This shows that the ACPR value has the highest number of repetitions at these points. Between the three mentioned points, there are areas in which no data is detected. The number of these areas could have increased if longer sequences were had been selected. This special behavior is also seen in ORDs and is a result of how ACPR is calculated. The average value and distribution pattern of ACPR for Chameleon sequences is very similar to ordered sequences and distinct for intrinsically disordered sequences.

The second feature studied was hydropathy, which is one of the most important properties of amino acids, i.e. their hydrophilicity and hydrophobicity. Hydrophobic residues tend to be within protein while hydrophilic residues tend to be at the protein surface and exposed to the solvent. As shown in Fig. 2, chameleon sequences mostly contain hydrophobic sequences because they have positive hydropathy and have hydropathic distribution similar to ORDs. However, there is a slight deviation from the distribution of hydropathy in these sequences compared to the ordered sequences.

IDRs sequences have often low hydropathy, i.e. hydrophilic sequences, so these sequences do not have the conditions to fold²⁷. Therefore, it is expected that more chameleon sequences will be located in the inner parts of the protein. However, considering the frequency of hydropathy in these sequences, which is 0.5, it may be better to consider them as a neutral sequence that changes its structure under special conditions. Thus, when the helix or sheet structure is transformed into a turn structure, which is classified as a coil, hairpin structures are created. The newly modified conformation can be responsible for changes in protein folding ²⁸, changes in protein function, changes in molecular recognitions, and promote protein aggregations leading to various diseases ²⁹. When the structure of the hair pin is placed on the surface of the protein, it can change the protein-protein interactions and lead to protein aggregation. The strong tendency of hair-pin structures in forming aggregates cause them to initiate formation of oligomers and fibrils resulting in aggregates. Several studies have shown that hairpin structures play critical role in the wrong folding of proteins that have strong tendency for fibril formation ^29,30. On the other hand, some of hairpin structures can prevent the formation of fibrils ^31,32. Hairpin structures therefore, play a dual role. More research is needed into the role of chameleon sequences that have the herpin structure, create fibrils, or prevent them.

The third feature studied in this section was the examination of the charge-hydropathy diagram. We compared the differences between Chameleon sequences and intrinsically disordered and ordered sequences in our study, considering absolute charge and hydropathy. It is clear that the charge-hydropathy distribution in the case of Chameleon sequences and ordered sequences are different from the position occupied by IDRs.

Chameleon sequences have charge -hydropathy distribution centers close to ordered sequences. In fact, the charge -hydropathy ratio and the values of these properties are generally similar to ordered sequences but intrinsically disordered sequences are found in a space with high net charge and low hydrophobicity. This is the third reason to show that chameleon sequences have properties close to ordered sequences that have been able to change structure under certain conditions.

Study of dihedral backbone angles is another way to investigation the nature and characteristics of protein and peptide structure. Dihedral angles provide a description of local conformations.

Local structural information constrains the possible conformations that can be generated from a sequence. Therefore, it narrows the conformational space of a polypeptide chain³³. Secondary structures are regular structures in proteins. The secondary structural changes by dihedral angle fluctuation and in a deeper level, happen by formation and breaking of hydrogen bonds. These changes are dynamic phenomenon that actually has to be addressed through simulations and laboratory studies such as spectroscopic methods.

Dihedral angle information is also used to study two conformations of a protein. This is done by dihedral transition analysis. Using it, stable fragment and transition fragment are identified and separated[36]. Dihedral angles create distinct regions in a 2D diagram. The classic Ramachandran diagram has three separate regions: α-ahlix, β-sheet and left -handed α Helix. However, the Ramachandran diagram obtained from experimental data has more areas. Each group of researchers according to their logic has divided the chart into different regions that sometimes are not compatible. There are mainly 3 regions, alpha helices region, beta region, and polypeptide II area (PII), and PII′, γ, γ′, ζ, δ, δ′ regions defined for Ramachandran experimental diagrams, and one low-density region called epsilon introduced by Karplus ²³. To study the structure of chameleon sequences and compare them with ordered and disordered sequences, we also used phi and psi angles and Ramachandran diagram. Phi and psi angles of each residue were extracted from the DSSP database and the Ramachandran diagram of the Chameleon sequences was generated. As can be seen in Fig. 4, the Ramachandran diagram was drawn for each amino acid in the Chameleon sequence. While this diagram has many scattered points, the areas mentioned above are clearly visible in Figs. 4. According to Figs. 4A ,B and C, the γ and γ′ the polypeptideII, and the ε contain both the phi and psi angles of the chameleon sequences, which are classified as coils. Between the alpha helix area and the beta sheet area, there is an area that belongs to a variety of turns. Since the turns are in the group of coils in this category, this area is covered by them. Next, the mean of phi and psi angles for each chameleon sequences with directional statistic was calculated and shown in Fig. 5. ^22,34,35. The distribution centers of the created clusters of Fig. 5 were also calculated. The mean of phi and psi of chameleon sequences with helix structure are slightly different from the mean of these angles in the classical diagram and are close to the mean values of the experimental diagram. Ordered helix and sheet sequences are sequences that do not have chameleon properties and do not change their structure according to the environment. The values of phi and psi angles relative to ordered helices in theory are (-57,-47) and in experimental data (-63,-43).

The values of phi and psi angles in the ordered sequences selected in this work were ( -66,-33) .Chameleon sequences with helix that can adopt sheet structure or coil structurec (H-EH and H-CH) had phi and psi angles (-64,-40) and (-65,-39) respectively.

As can be seen in Fig. 6, the distribution center of chameleon sequences dihedral angles with helix structure is very close to the distribution center of the ordered helix sequence, but slightly different from the ordered structure also the distrib2ution center of chameleon sequences dihedral angles with sheet structure is very close to the dis2224tribution center of the ordered sheet sequence, but slightly different from the ordered structure. Perhaps this slight deviation of the dihedral angles of the Chameleon sequences from the dihedral angles of the ordered sequences has caused the potential to change the structure of the Chameleon sequences and makes favorable conditions so that chameleon sequences can change their structure. As shown in Fig. 5, the phi and psi angles for each of the Helix and Sheet chameleon sequences are in the allowed regions of the Ramachandran diagram and are quite different from the Ramachandran diagram of the IDRs. The Ramachandran diagram for IDRs is more like this diagram for coils ³⁶. Thus, as can be seen from Figs. 4, 5, and 6, the chameleon sequences are structurally similar to the structures of the ORDs sequences. These diagrams show a slight deviation in the phi and psi angles from the order sequences, allowing the Chameleon sequences to be restructured and to adopt a new secondary structure in a suitable environment.

Chameleon sequences are a type of flexible sequences that take different secondary structure in different environments. These sequences are found in homologus and non homologus proteins. In order to understand the characteristics of these types of sequences, we examined physicochemical and structural properties of these sequences. We compared chameleon sequences with IDRs and ordered sequences. ACPR values in chameleon sequences with 5–12 in length are often in points

0, 0.2 and 0.4.Unlike intrinsically disordered sequences that have high charge with different values.

In terms of hydropathy, chameleon sequences show a significant difference with intrinsically disordered sequences and are not as strictly hydrophilic.Examining these two parameters in a two-dimensional diagram, we show that chameleon sequences are closer to ordered sequences than intrinsically disordered sequences.

Observing the structural features of these sequences, by calculating the dihedral angles, shows that the region where the chameleon helixes are located is closer to the region of the sheets and coils in the Ramachandran diagram, which can indicate the cause of transition in these structures.In general, flexible structures can be considered as a spectrum, the most flexible of which are disorder sequences. Chameleon sequences are a type of them that is closer to ordered sequences. That is, they have less flexibility. There are probably sequences with different flexibilities that need to be explored.

Acknowledgements

This work was supported by the university of Tehran.

Competing interests
The author(s) declare no competing interests.

Author Contributions Statement

Z. Shahmirani: Did the work and wrote the manuscript
B. Goliaei: Supervised the work, edited the manuscript, and submitted.
G. Bahramali: Advised the work.
Z. Miucheher: Co-supervised the work.
SS. Jafaripour: Discussed the work.
SP. Shariatpanahi: Co-advised the work.

Data Availabilty

All data generated or analysed during this study are included in this published article and its supplementary information file.

1-PISCES (http://dunbrack.fccc.edu/PISCES.php)

Wang G, Dunbrack RL Jr. Wang G, et al. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W94-8. doi: 10.1093/nar/gki402. Nucleic Acids Res. 2005. PMID: 15980589 Free PMC article.

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3-ProtParam (https://web.expasy.org/cgi-bin/protparam/protparam)

Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D., Bairoch A.;

Protein Identification and Analysis Tools on the Expasy Server;

(In) John M. Walker (ed): The Proteomics Protocols Handbook, Humana Press (2005).pp. 571-607

4-DSSP(https://swift.cmbi.umcn.nl/gv/dssp/)

Kabsch W, Sander C (1983). "Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features". Biopolymers. 22 (12): 2577–637.

5-R (https://www.r-project.org/)

R version 4.1.0 (2021-05-18)

Authors Information

Zohre Shahmirani¹; 1-Laboratory of Biophysics and Molecular Biology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. [email protected].

Bahram Goliaei; Laboratory of Biophysics and Molecular Biology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. [email protected]

Golnaz Bahramali; Pasteur Institute of Iran, Tehran, Iran. [email protected]

Zarrin Minuchehr; NIGEB, Tehran, Iran. [email protected].

Sedighe Sadat Jafaripour; Laboratory of Biophysics and Molecular Biology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. [email protected].

Seyed Peyman Shariatpanahi; Laboratory of Biophysics and Molecular Biology, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. [email protected]

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Chameleon Sequences: Ordered or Disordered

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