Terminal Modifications

Charge and pI calculations use the IPC_peptide pKa set (Kozlowski, 2016). Results are theoretical approximations — always verify with experimental data.

ℹ️ Frequently Asked Questions

How is peptide net charge calculated?

The net charge is computed using the Henderson-Hasselbalch equation for each ionizable group. Positive charge contributors include the N-terminal amino group and basic side chains (His, Lys, Arg). Negative charge contributors include the C-terminal carboxyl group and acidic/polar side chains (Asp, Glu, Cys, Tyr).

Positive: charge = +1 / (1 + 10^(pH − pKa))
Negative: charge = −1 / (1 + 10^(pKa − pH))

Total net charge is the sum of all individual group charges.

Why does net charge matter for my experiments?

Net charge at your working pH directly affects peptide solubility, aggregation tendency, membrane interaction, chromatographic behavior, and electrophoretic mobility.

Peptides near their pI (net charge ≈ 0) tend to have minimum solubility and may aggregate. For ion-exchange chromatography, knowing the charge at your buffer pH determines whether the peptide binds to cation or anion exchange resins.

How do terminal modifications affect charge?

N-terminal Acetylation caps the free amino group, removing its positive charge contribution (pKa 9.564). At physiological pH, this eliminates approximately +1 charge.

C-terminal Amidation converts the carboxyl to an amide, removing its negative charge contribution (pKa 2.383). At physiological pH, this eliminates approximately −1 charge.

Which pKa set does this calculator use?

This calculator uses the IPC_peptide pKa set (Kozlowski, 2016), optimized on 16,882 experimental peptide pI measurements.

NH₂ = 9.564 · COOH = 2.383
Asp = 3.887 · Glu = 4.317 · His = 6.018
Cys = 8.297 · Lys = 10.517 · Tyr = 10.071 · Arg = 12.503

doi:10.1186/s13062-016-0159-9

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