Peptide Net Charge Calculator | pH, pI & Amino ... - Pearson

Calculate a peptide’s net charge at any pH, identify which amino acid groups are protonated or deprotonated, estimate the isoelectric point (pI), and see how charge changes across pH.

Background

Peptides gain or lose charge because the N-terminus, C-terminus, and some amino acid side chains can accept or donate protons. This calculator uses pKa values and Henderson–Hasselbalch logic to estimate the peptide’s average net charge at a selected pH.

How to use this calculator

• Enter a peptide sequence using one-letter amino acid codes, such as ACDEK.
• You can also enter three-letter codes, such as Ala-Lys-Asp-Gly.
• Enter the pH where you want to estimate the peptide charge.
• Choose fractional charge for a more realistic Henderson–Hasselbalch estimate.
• Review the contribution table to see which groups make the peptide positive, negative, or neutral.

How this calculator works

• The N-terminus is treated as a basic group that can contribute up to +1 charge.
• The C-terminus is treated as an acidic group that can contribute up to −1 charge.
• Acidic side chains such as Asp, Glu, Cys, and Tyr become more negative as pH rises above their pKa.
• Basic side chains such as His, Lys, and Arg become less positive as pH rises above their pKa.
• The net charge is the sum of all terminal and side-chain charge contributions.
• The estimated pI is the pH where the peptide’s calculated net charge is closest to zero.

Formula & Equations Used

Basic group average charge: charge = +1 / (1 + 10^(pH − pKa))

Acidic group average charge: charge = −1 / (1 + 10^(pKa − pH))

Net peptide charge: net charge = sum of all group charges

Isoelectric point estimate: pI ≈ pH where net charge = 0

Example Problems & Step-by-Step Solutions

Example 1 — Estimate peptide charge at physiological pH

Find the approximate charge of KDEH at pH 7.4.

1. The N-terminus is mostly protonated, so it contributes close to +1.
2. The C-terminus is mostly deprotonated, so it contributes close to −1.
3. Lys contributes close to +1.
4. Asp and Glu each contribute close to −1.
5. His is only partly protonated near neutral pH.
6. The peptide is expected to have a slightly negative net charge.

Example 2 — Acidic peptide

A peptide such as DDEEEE at pH 7 is strongly negative because most acidic side chains are deprotonated.

Example 3 — Basic peptide

A peptide such as KKRH at pH 7 is positive because Lys, Arg, and part of His can carry positive charge.

Frequently Asked Questions

Q: What is peptide net charge?

Peptide net charge is the total charge from the N-terminus, C-terminus, and ionizable amino acid side chains at a specific pH.

Q: Why does peptide charge depend on pH?

Ionizable groups gain or lose protons depending on the pH relative to their pKa values.

Q: Is fractional charge more accurate than integer charge?

Yes. Fractional charge estimates the average protonation state, especially when pH is close to a group’s pKa.

Q: What is the isoelectric point?

The isoelectric point, or pI, is the pH where the peptide’s net charge is approximately zero.

Q: Can this calculator handle modified amino acids?

This version is intended for standard amino acids. Modified residues may require custom pKa assumptions.