Number of failed synthesis rules exceeds 5

[lukeke1]

Hello, during the process, I found that more than five rules did not comply with the synthesis rules, resulting in “6 synthesis rules failed out of 5”.

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The main peptide sequence is: VAIAARKMKCGLSSPALRPSTRRSQVA
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Calculated properties:
Net charge at pH 7: 5.952607720851725
Molecular weight: 2855.441999999994
Average Hydrophobicity: -4.329999999999997
Isoelectric Point: 12.00885009765625
Instability index: 115.47407407407404
Number of hydrogen bond acceptors: 42
Number of hydrogen bond donors: 47
Crippen LogP: -16.19382000000007
3 solubility rules failed from 5. The rules violated are the number(s): 1,2,3. *For details of the rules see the last part of the report.
6 synthesis rules failed from 5. The rules violated are the number(s): 8,17,18,19,20,31. **For details of the rules see the last part of the report.
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Explanation of the calculated parameters:

• Net charge: average net charge based on pka values of each amino acid. By default a pH=7 is used.
• Molecular weight: calculated in g/mol using the SMILES representation of the peptide.
• Average Hydrophobicity: calculated by averaging the values of each amino acid hydrophobicity value from the Eisenberg scale.
• Isoelectric point: obtained from the ProtParam package of the expasy server.
• Instability Index: from ProtParam. It provides an estimate of the stability of the peptide in a test tube. Values smaller than 40 is predicted as stable, a value above 40 predicts as unstable.
• Number of hydrogen bond acceptors: calculated using the SMILES representation of the peptide.
• Number of hydrogen bond donors: calculated using the SMILES representation of the peptide.
• Crippen LogP: estimation of the octanol/water partition coefficient using the Ghose/Crippen approach available in the RDKit project.
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The last two results are the number of solubility and synthesis rules violated. The higher the number of rules violated, the lower the probability to be solubilized or synthesized experimentally (https://bioserv.rpbs.univ-paris-diderot.fr/services/SolyPep/).

*List of solubility rules violations:

1. Discard if the number of charged and/or of hydrophobic amino acids exceeds 45%
2. Discard if the absolute total peptide charge at pH 7 is more than +1
3. Discard if the number of glycine or proline is more than one in the sequence
4. Discard if the first or the last amino acid is charged
5. Discard if any amino acid represents more than 25% of the total sequence

**List of synthesis rules violations:

1. Discard if 2 prolines are consecutive
2. Discard if the motifs DG and DP are present in the sequence
3. Discard if the sequences ends with N or Q residues
4. Discard if there are charged residues every 5 amino acids
5. Discard if there are oxidation-sensitive amino acids (M, C or W)

[PEHGP]

Modify lines 578 to 586 of pepfun.py as follows：

for residue in self.sequence:
    counter_charged += 1
    if residue in charged_residues:
        counter_charged = 0
    if counter_charged >= 5:
        self.synthesis_rules_failed+=1
        self.set_syn_rules.append(1)
        break
else:
    self.set_syn_rules.append(0)