How to Draw Peptide Chains

Amino acid chains, otherwise known as peptide chains, are an integral part of an organic chemistry student’s knowledge. If you’re like me, following the professor’s instruction on how to draw these molecules was rather difficult. Since I don’t want other organic chemistry students muddling through like I did, here’s an instructable on how to draw peptide chains by hand. We’ll also review the basic purpose of amino acids and some of the fun things you can do with your newfound o-chem drawing skills; for example, I spelled out my friend's name in amino acids as her Christmas gift since she's also a major chemistry nerd. The options are limitless, so buckle up and get ready for quite a ride!

Recommended previous knowledge:

• Basic organic chemistry knowledge. All the diagrams will be drawn using the bond line method, since this saves time when drawing molecules.
• Knowledge of organic chemistry terminology (amines, amides, carbonyls, etc.)

Tools you’ll need:

• A writing utensil of some sort, preferably a pencil
• An eraser. You will make a lot of mistakes initially, especially at getting everything to fit together properly
• Patience and lots of it. Until you get the hang of this, drawing peptide chains is a time consuming and aggravating process

Estimated Time:

• 20 minutes for a 5 acid long chain at the beginning. Once you're more familiar with the process, it should only take you 3 to 4 minutes for a 5 acid long chain

Benefits:

• You’ll be able to do these types of problems correctly on your exams and homework
• You can impress a date with your rad o-chem knowledge
• You can write secret codes to your buddies in amino acids

Amino acids are often referred to as the building blocks of life and for good reason. Every protein in your body is made up of gigantic combinations of amino acids. Without amino acids, life could not exist. Each amino acid consists of a small molecule that has an amine on one end and a carbonyl group on the other. We’ll talk about the other parts of their structure in a minute.

Peptides are short chains of connected amino acids. “Short” in this case is relative; generally in order for a chain of amino acids to be classified as a peptide it can have at most 50 amino acids. Amino acid chains that are longer than that are called polypeptides. Don’t worry though, we’ll only draw chains that are at most five or six acids long. The process for drawing longer chains is the exact same, just more tedious.

Backbone: This is the main structure of the amino acid. Everything fun that we do to draw the amino acids starts here.

Functional Groups: These are sections of the molecule that define what type of amino acid we’re working with. Some are easier to draw than others, but most are relatively simple.

Every amino acid that we’re covering in this tutorial starts out with the same basic structure (picture 1). On one end there is an amine and on the other end is a carbonyl. When drawing an individual amino acid, the amine will be positively charged and the carbonyl will be negatively charged. However, as our amino acids are exposed to different environments (e.g. acidic or basic), these charges may change.

Amino acids can be distinguished from each other by their functional groups. These always connect in the same spot on the backbone, which is surrounded by the dashed circle in the second picture.

This is where things begin to get a little tricky. Now that you’ve mastered how to draw the backbone of one amino acid, let’s try adding on another one.

First draw your standard amino acid backbone, but leave the O- off of the carbonyl end (picture 1); this will become the attachment point for the amine end of the next amino acid. Continue this pattern over and over until you reach the desired length of your peptide chain (pictures 2 and 3)

When you've reached the desired chain length, just add on that O- that we ignored before (picture 4)

A good way to tell if you’ve got enough backbone structures in your chain is to count the number of nitrogens. If your chain is supposed to be 6 amino acids long, then there should be 6 backbone nitrogens in your chain.

Once the backbone is drawn, we can add in the functional groups.

There are many different amino acids, but there are only twenty that are considered essential for life to exist.

Each amino acid can be designated by its name, a three letter code, and a one letter code. Historically, the three letter code was the standard, but organic chemists around the world are moving towards using the one letter codes instead. I am only including the structure, full name, and one letter code for each amino acid in this tutorial, as well as any tips or tricks I have to help you remember which amino acid is which. I've attached a table of all of them, but it can be difficult to work with, so I’ll also be breaking this section up into a few following substeps so it’s easier to find the picture of the particular amino acid you’re looking for.

(Picture Source: http://www.nbs.csudh.edu/chemistry/faculty/nsturm/CHE450/04_AminoAcidsProteins.htm)

Glycine (G): This amino acid has the back bone structure with no extra frills

Alanine (A): This one is the second simplest. Each amino acid gets more complicated from here on out.

Nucleophile has a specific meaning in organic chemistry terms, but that's outside the scope of this tutorial so here it's just a classification.

Serine (S)

Threonine (T)

Cysteine (C)

These amino acids have large carbon branches, which means they are nonpolar and don't interact well with water, hence the term hydrophobic. We'll talk about four of them here and the fifth a bit later, since it's kind of a special case.

Valine (V): This one's functional group looks like a V, which makes it easier to remember.

Leucine (L)

Isoleucine (I): This one has the same molecular formula as leucine, but has a slightly different functional group structure.

Methionine (M): This one has a sulfur (aka a thiol) with a methyl group as the functional group, hence the name methionine

Each of these amino acids have an aromatic ring in the functional group.

Phenylalanine (F)

Tyrosine (Y)

Tryptophan (W): Fun fact, this is the stuff that makes you really sleepy after eating a lot of turkey.

These amino acids have carboxylic acids in their functional groups, which is why their names are slightly different.

Aspartic acid (D)

Glutamic acid (E)

Note that these amino acids can have changes in charges and protonation depending on the environment they are in, so watch out for that.

An easy way to remember the structure of these two amino acids is that their structures are very similar to the to the acidic ones we just talked about. The only difference is that their functional groups end in amides instead of carboxylic acids; meaning there's an NH2 at the end instead of an OH.

Asparagine (N)

Glutamine (Q)

Like with the acidic ones a couple steps back, these amino acids are in their unreacted form and could have changes in charge or protonation depending on their environment.

Histidine (H)

Lysine (K)

Arginine (R)

Proline (P) would normally be classified as one of the hydrophobic amino acids, but since its structure is rather odd we're going to talk about down here instead. Proline is interesting because its functional group connects back to the nitrogen. This particular property makes proline rather useful for creating beta turns, which we will discuss in a little bit.

You can now draw a straight chain of amino acids! With your newfound knowledge you can spell out short words and do most of your amino acid homework problems. For example, the amino acid depicted above spells out "CAKE". Pretty sweet, huh?

There is one more technique to learn however before you will be fully capable of drawing all sorts of peptides, so stay tuned. We're almost there.

Now as cool as it is for peptides to be in straight chains, if that was the only form they existed in they wouldn't be able to become proteins, much less fit in our bodies. In order to get around this, many peptide chains adopt secondary structures to take up less space. These secondary structures are things like folding the chain repeatedly or curling the chain into a helical shape.

The above picture shows different examples of secondary structure in proteins and peptide chains. As you can probably guess, alpha helices are the ones that are in helical shapes. Beta sheets, another type of secondary structure, are depicted as flat ribbons in the picture. There are some other secondary structures evident in the picture, but we won't concern ourselves with those.

Alpha helices and complete beta sheets are rather tedious to draw, but many professors expect their students to be able to draw beta turns which are the main components of a beta sheet, so we'll learn those next.

(Picture Source: http://biomedicalcomputationreview.org/content/cre...)

After you have drawn all of the section of the peptide that you want to be straight, begin the turn by angling the next amino acid about 30 degrees either up or down. Continue to curve the rest of that particular amino acid until the carbonyl end is nearly perpendicular to the straight section of the chain.

I've attached a picture of the beginnings of a beta turn that uses proline as well because this was something that gave me trouble when I took organic chemistry. The general idea is the same, but the way that the proline connects back onto itself can be a bit tricky.

Continue with the next amino acid. The side with the nitrogen should be approximately perpendicular to the straight section, but the amino acid should begin bending back to be parallel to the original section near the functional group. It should only take two amino acids to complete the turn. Now you can get back to drawing the next straight segment!

A few general notes:

• When drawing a peptide chain, only the amine and carbonyl on the ends should have a positive or negative charge (picture 1). If remembering to do this bugs you, you can draw the ends as an NH2 and OH. This indicates that the peptide chain is in a completely neutral solution, which isn't often the case.
• The nitrogens inside the peptide chain backbone will be neutrally charged and only have one hydrogen attached. The only exception to this rule is proline, which has no hydrogens attached to its nitrogen since it is already connected to its own functional group.
• Remember to check whether the environment is acidic or basic since this will affect some of the functional groups as we have talked about previously

A few notes on beta turns:

• If your ketones are not across from each other and either pointing towards each other or away from each other, then you haven't drawn the turn correctly.
• Wherever you have an amine or ketone in the backbone it should have a matching one on the other side of the turn (picture 2).
• You may be asked to draw a beta turn that involves disulfide bonds. In order for this to work, the two amino acids with the sulfurs will need to be across from each other. Instead of the functional groups crowding each other, you connect the two with a bond between the two sulfurs. Chemically, this is important because it adds stability to the beta sheet. Drawing wise, it's just a pain.

Congratulations! You now are able to draw peptide chains and use them for all sorts of things. You can do well on tests, write in secret codes, or do what I did and write my friend's name in amino acids. Go forth and use your knowledge! You can do this!