Polar amino acids have side chains that attract water. Serine, threonine, asparagine and glutamine are polar and uncharged. Aspartate and glutamate are acidic and negatively charged at neutral pH. Lysine, arginine and histidine are basic and can carry a positive charge. The rest, such as leucine and valine, are nonpolar and avoid water.
- Polarity is set by the side chain (R group); polar side chains can hydrogen-bond with water.
- Serine, threonine, asparagine and glutamine are polar and uncharged at neutral pH.
- Aspartate and glutamate are acidic and negative; lysine and arginine are basic and positive at neutral pH.
- Histidine's side chain has a pKa near 6, so it is only partly charged at neutral pH.
- The Kyte-Doolittle hydropathy scale (1982) ranks arginine most hydrophilic and isoleucine most hydrophobic.
What makes an amino acid polar
Think of it like oil and water at a party. Some guests happily mix with the water crowd, and some huddle together to avoid it. Polar amino acids are the ones that mix, because their side chains can share or attract water through charges and hydrogen bonds.
Every amino acid has the same backbone: an amine group, a carboxyl group and a hydrogen on a central carbon. What differs is the fourth group, the side chain, also called the R group. The side chain decides how the amino acid behaves, and polarity is the most important part of that behavior.
A side chain is polar when it contains atoms that pull electrons unevenly, usually oxygen or nitrogen bonded to hydrogen. Those groups can form hydrogen bonds with water, so the side chain is comfortable in an aqueous environment. A nonpolar side chain is made mostly of carbon and hydrogen, which share electrons evenly and cannot hydrogen-bond with water, so it tends to be pushed out of water and toward other nonpolar groups.
Our guide to the R group in amino acids covers side chain structure in detail. This page focuses on sorting the twenty standard amino acids by polarity and charge, and on why the sorting matters.
- Polar uncharged: Ser, Thr, Asn, Gln
- Acidic and negative: Asp, Glu
- Basic and positive: Lys, Arg, His
- Borderline: Cys, Tyr
- Nonpolar: Gly, Ala, Val, Leu, Ile, Met, Phe, Trp, Pro
The polar amino acids, sorted by charge
Standard biochemistry texts divide the twenty common amino acids into four groups by side chain. The grouping of a few borderline residues varies between textbooks, and the notes below say where.
Polar, uncharged at neutral pH: serine (Ser, S), threonine (Thr, T), asparagine (Asn, N) and glutamine (Gln, Q). Serine and threonine carry hydroxyl groups; asparagine and glutamine carry amide groups. Cysteine (Cys, C) and tyrosine (Tyr, Y) are often placed here too, although cysteine's thiol is only weakly polar and tyrosine's large aromatic ring gives it a partly nonpolar character.
Acidic, negatively charged at neutral pH: aspartate (Asp, D) and glutamate (Glu, E). Their side-chain carboxyl groups lose a proton near neutral pH and carry a negative charge.
Basic, positively charged at neutral pH: lysine (Lys, K) and arginine (Arg, R) are reliably positive. Histidine (His, H) is basic but only partly charged at neutral pH, because its side chain has a pKa around 6, so it can switch between charged and uncharged forms near physiological conditions.
Nonpolar: glycine (Gly, G), alanine (Ala, A), valine (Val, V), leucine (Leu, L), isoleucine (Ile, I), methionine (Met, M), phenylalanine (Phe, F), tryptophan (Trp, W) and proline (Pro, P). Glycine, with only a hydrogen as its side chain, is sometimes listed separately.
Measuring polarity: hydropathy scales
Polarity is not strictly on or off. Some side chains are far more water-loving than others, and researchers use hydropathy scales to put numbers on the difference. The best known is the Kyte-Doolittle scale, published in 1982, which assigns each amino acid a value from strongly hydrophilic to strongly hydrophobic.
On that scale arginine sits at the most hydrophilic end and isoleucine at the most hydrophobic end, with the others spread between. Averaging the values over a stretch of sequence produces a hydropathy plot, which highlights regions of a protein likely to be buried or embedded in a membrane, and regions likely to face water.
For a short peptide, the same idea gives a quick first estimate of how it will behave. A sequence dominated by polar and charged residues is usually easy to dissolve in water. A sequence dominated by nonpolar residues often needs a small amount of organic solvent first, which is why solubility guidance for hydrophobic peptides differs from that for charged ones.
Charge adds a second number. Adding up the positive and negative side chains, plus the two terminal groups, gives the net charge at a given pH. A peptide with a strong net charge usually dissolves more readily than one near zero net charge, because like charges keep the molecules apart.
A useful memory aid is to group by what the side chain ends in. Hydroxyls and amides, the polar uncharged group; extra carboxyls, the acids; extra nitrogens that take a proton, the bases; plain hydrocarbons and aromatic rings, mostly nonpolar.
Why polarity matters for peptides and proteins
Polarity drives the folding of proteins. In water, nonpolar side chains tend to gather in the interior of a folded protein, away from the solvent, while polar and charged side chains line the surface. This hydrophobic effect is one of the main forces that give a protein its shape.
Charged side chains do more specific work. Opposite charges can pair to form salt bridges that stabilize structure, and charged residues often sit at binding sites where they recognize other molecules. Polar uncharged residues form hydrogen bonds that hold helices and sheets together and help proteins interact with water and with each other.
For short research peptides, polarity shows up most in the practical questions: will it dissolve, will it stick to surfaces, and how will it run on a chromatography column. In reversed-phase HPLC, the standard purity method, nonpolar peptides are held longer on the column and elute later, while polar peptides come off sooner. The order of peaks on a chromatogram therefore reflects polarity directly.
Polarity also affects storage. Peptides rich in charged and polar residues can pull moisture from the air, which is why sealed, dry storage matters. Our guide to storing lyophilized peptides covers that side.
The awkward cases: cysteine, histidine, tyrosine and proline
Four amino acids refuse to sit neatly in one group, and they are worth knowing because they show up constantly in research peptides.
Cysteine carries a thiol group, sulfur bonded to hydrogen. Sulfur is less electronegative than oxygen, so the group is only weakly polar. Its real importance is chemical: two cysteines can join through their sulfur atoms to form a disulfide bond, which locks parts of a peptide together. Peptides such as oxytocin depend on exactly that bond for their ring structure.
Histidine has an imidazole ring with a pKa close to 6. Near neutral pH a meaningful fraction is charged and the rest is not, and small changes in pH shift the balance. That switching is why histidine often appears at the active sites of enzymes, and why its charge state depends so strongly on the buffer.
Tyrosine has a hydroxyl group on a large aromatic ring. The hydroxyl is polar, the ring is not, so tyrosine behaves as a mixture of both and is listed differently in different textbooks. Its ring also absorbs ultraviolet light near 280 nm, which laboratories use to estimate protein concentration.
Proline is nonpolar, but its side chain loops back to bond with its own backbone nitrogen, forming a ring. That rigid ring bends the chain and breaks helices, so proline shapes structure more than polarity alone would suggest.
Reading a sequence for polarity
With the groups above, a short sequence can be read for polarity at a glance. Mark each residue as polar uncharged, acidic, basic or nonpolar, count each group, and note the net charge at neutral pH. That quick tally answers most first questions about how a peptide will dissolve and how it will behave on a column.
Take a short example written in one-letter code. A sequence such as KPV contains lysine, which is basic and positive, proline and valine, which are nonpolar. It carries a positive side-chain charge plus its terminal groups, and its small size keeps it manageable in water. A long stretch of leucines and isoleucines would read very differently, pointing toward poor water solubility.
This kind of reading is a starting point, not a measurement. The certificate of analysis for a lot is what confirms identity and purity. Our guide to reading a peptide COA explains what it should show.
FOR LABORATORY AND IN-VITRO RESEARCH USE ONLY. NOT FOR HUMAN OR ANIMAL CONSUMPTION.
Common questions
Which amino acids are polar?
Is glycine polar or nonpolar?
What is the difference between polar and charged amino acids?
Why do polar amino acids face the outside of proteins?
More science guides
Sources
- Kyte and Doolittle, A simple method for displaying the hydropathic character of a protein, Journal of Molecular Biology, 1982. The hydropathy scale used to rank amino acid side chains.
- Berg, Tymoczko and Stryer, Biochemistry, 5th edition, section on amino acids (NCBI Bookshelf). Standard grouping of the twenty amino acids by side chain character.
- Alberts et al., Molecular Biology of the Cell, The Shape and Structure of Proteins (NCBI Bookshelf). How polar and nonpolar side chains distribute during protein folding.
- IUPAC-IUB Nomenclature and Symbolism for Amino Acids and Peptides. Three-letter and one-letter codes used throughout.
