Exploring Biological Molecules: Amino Acids, Protein Structure, and Function

Coronavirus Spike Protein

Proteins: Practical Polymers

Protein molecules are the workhorses of biological systems - they fulfill a dizzying number of functions. They can function as enzymes, signalling molecules, structural elements, and many more roles besides.

This is only possible because of their highly diverse structures, which are created by interactions between the R groups of different amino acid residues in their polypeptide chains.

Key Terms:

Before we delve into the intricacies of protein structure, let's define some key terms:

1. Amino Acid: The basic building block of proteins, consisting of a central carbon atom bonded to an amino group, a carboxyl group, a hydrogen atom, and a side chain (R group). The side chain is the bit that varies between different amino acids.

2. Peptide Bond: The covalent bond formed between the amino group of one amino acid and the carboxyl group of another amino acid during protein synthesis.

3. Residue: The amino acid after it has been joined to a chain by (a) peptide bond(s).

4. Protein / Peptide / Polymer: A peptide is a short chain of amino acids linked by peptide bonds. Because it is made from linking similar submits together, it is an example of a polymer. A polypeptide is a long peptide chain. A protein is a very long polypeptide, often with hundreds of amino acid residues.

5. Levels of Protein Structure: The hierarchical organisation of protein molecules, including primary, secondary, tertiary, and quaternary structures.

6. Electrostatic Interactions: Polar and charged groups can form electrostatic interactions with water molecules and each other. These are very important for protein structure, binding, and function.

7. Hydrogen Bond: A weak electrostatic attraction between a hydrogen atom bonded to an electronegative atom (e.g., oxygen or nitrogen) and another electronegative atom. Protein secondary structures are stabilised by hydrogen bonds.

8. Ionic Bonds: Electrostatic interactions between charged groups. Important for protein tertiary structures, binding and function.

9. Hydrophobic Interactions: Non-polar groups can’t form electrostatic interactions with water. Avoiding water leads them to interact with each other. These interactions are important for protein tertiary structures, binding, and for locating proteins within membranes.

10. Disulfide Bonds: Covalent bonds formed between the sulfur atoms of two cysteine residues within a protein molecule. These are important for protein tertiary and quaternary structures.
    
    

The amino acid Asparagine. The amino group is shown sticking up at the top. The carboxyl group is to the right, and the R group (CH2-CO-NH2) is sticking out to the left.

General Structure of an Amino Acid:

Amino acids are organic compounds composed of a central carbon atom (the alpha carbon) bonded to four groups: an amino group (NH2), a carboxyl group (COOH), a hydrogen atom (H), and a side chain known as the R group.

The R group varies among different amino acids. R groups can be hydrophobic, polar, or charged. The size, shape and potential for electrostatic and covalent interactions determine how each amino acid residue interacts with its environment.

Synthesis and Breakdown of Polypeptides:

During protein synthesis, amino acids are linked together through peptide bonds to form peptides and proteins.

Peptide bonds are formed through a condensation reaction between the amino group of one amino acid and the carboxyl group of another amino acid, resulting in the release of a water molecule.

Conversely, hydrolysis breaks peptide bonds by adding a water molecule, separating the amino acids.

Levels of Protein Structure:

Proteins exhibit four levels of structural organisation:

Lipocaine protein. Its secondary structures of alpha helix (yellow) and beta sheet (blue) are packed together to form a tertiary structure.

• Primary Structure: The linear sequence of amino acid residues in a polypeptide chain. The primary structure can be written down as a simple sequence of letters where each letter codes for a type of amino acid.

• Secondary Structure: Repeated patterns of folding involving the polypeptide backbone. The most common types of secondary structure are alpha helices and beta sheets. Secondary structures do not directly involve R groups; they are stabilised by hydrogen bonding beween atoms of the polypeptide backbone.

• Tertiary Structure: The overall three-dimensional shape of a single polypeptide chain. This usually involves packing elements of secondary structure together to form the overall structure. Tertiary structure is determined by interactions between amino acid side chains. These often include hydrophobic interactions, and can also include hydrogen bonding, disulfide bonds, and ionic bonds.

• Quaternary Structure: Arrangement of multiple polypeptide chains (subunits) in a protein complex, stabilized by the same types of interactions as tertiary structure.
  
  
  

Structure and Function of Globular Proteins:

Many proteins are compact, roughly-spherical proteins with hydrophilic surfaces and hydrophobic interiors. These are known as globular proteins. Examples of globular proteins include enzymes, transport proteins, and regulatory proteins.

• Haemoglobin: A conjugated protein with a quaternary structure of four globular protein subunits. Each subunit contains a heme prosthetic group, responsible for oxygen transport in red blood cells.

• Amylase: The enzyme in saliva that catalyses the breakdown of starch. This protein has one chain with three tertiary domains.

• Insulin: A peptide hormone consisting of two polypeptide chains connected by disulfide bonds. Insuling regulates blood sugar levels by promoting glucose uptake by cells. Insulin is synthesised as a single chain, and cut into two chains during processing.
  
  
  

Summary:

• Amino acids are the basic building blocks of proteins.

• They are composed of a central carbon atom bonded to an amino group, a carboxyl group, a hydrogen atom, and an R group (side chain).

• Peptide bonds form between amino acids during protein synthesis, linking them together to form peptides and polypeptides.

• Proteins exhibit four levels of structural organisation: primary, secondary, tertiary, and quaternary structures.

• Protein struture is crucial for their function.

• Many proteins are globular proteins, with hydrophobic interiors and hydrophilic exteriors.

• Proteins can fulfill many functions, from structural roles to acting as enzymes, signalling molecules or membrane channels. And many other things besides.

So what type of molecule is made from amino acids and acts as a biological catalyst? Yes it’s a protein.

Key Concept: Polar and Charged Molecules

The similarites and differences between non-polar, polar and charged molecules (or parts of molecules) are really important. You must understand the difference between polar and charged molecules if you are going to make sense of molecular structure, and of the ways in which molecules interact.

If you’re unsure if water is a polar molecule or are wondering whether ions are polar, this article is for you.

This molecule is polar, but not charged. All is explained below.

Getting this topic straight in your mind will make it much, much easier to grasp key concepts like why glucose dissolves in water, why other things don’t, and how neurons and mitrochondria use membranes to create ion gradients for their function. And you’ll need to understand hydrogen bonding of polar groups to understand how DNA and proteins adopt defined structures.

The fact the molecules are called ‘polar’ and ‘charged’ is part of the problem - this can be pretty confusing! So don’t rely on their names to understand what’s going on.

Let’s start from scratch:

How are Polar and Charged Molecules different from Non-Polar, Uncharged Molecules?

All molecules contain atoms. And all atoms contain positively-charged nuclei and negatively-charged electrons.

In a non-polar, non-charged molecule, these positive and negative charges all neatly cancel each other out. As far as other nearby molecules are concerned, a non-polar molecule behaves as though it has no charges at all.

In both polar and charged molecules, the molecule has regions of positive and/or negative charges that can affect nearby molecules (or even other parts of the same molecule - as happens in proteins and DNA).

What’s the difference between Polar and Charged Molecules?

Polar molecules are charged-balanced overall but have unevenly distributed electrons. This gives them a little bit of a charge in certain places.

Charged molecules do have an overall charge. They have at leat one full unit of charge on at least one atom. (A unit of charge being equal to the magnitude of one electron).

You will also hear about polar and charged groups, which are a part of a larger molecule, where that part (group of atoms) has these properties.

Now, you might read that and think yes! I’ve got it! But to really understand it - and more importantly to remember it - you are going to need to linger a while and spend a bit of time thinking about this. It’s worth going through it all carefully step by step - this will also check your understanding. Have a good think about where those electrons are. Too many students trip up on this topic.

So let’s look at what it means to be non-polar, polar or charged. And then how that affects the behaviour of these molecules.

First step: What’s the difference between Unpolar and Polar Molecules

Atom

The atoms that make up molecules each have a postively-charged nucleus and a cloud of negatively-charged electrons.

Different types of atoms have different numbers of charges.

This means that even non-charged, non-polar molecules contain charges! They just cancel each other out so you don’t notice them.

Non-polar

When you make a molecule out of atoms, electrons are shared between neighbouring atoms. The electrons become one big shared cloud. This makes a covalent bond.

The diagram shows a non-polar molecule with two atoms. In a non-polar molecule, all the charges are balanced, cancelling each other out.

Because the charges are distributed evenly, and cancel out overall, the molecule behaves as though there are no charges (in terms of its electrostatic interactions with other nearby molecules).

So why are they called “non-polar”? To understand that, you need to understand what polar means.

Polar

It turns out that some types of atomic nuclei just LOVE electrons. Like, they are particularly greedy for them. Oxygen, for example.

These greedy atoms yank the electron cloud over towards their nucleus, away from the nucleus of the other atom.

The other atom no longer has enough negative charge to cancel out its positively-charged nucleus. While the greedy one has more negatively charged electrons than it needs.

The charges no longer cancel each other out. The other atom now has just a little bit of a positive charge, and the greedy one has just a little bit of a negative charge.

This is a polar molecule. Its atoms still share one electron cloud, so they are still covalently bonded. But the small charge in charge distribution mean it will now interact differently with its environment.

Overall, the charges still cancel out. They are just unbalanced so that there are places with just a little bit of charge.

Saying "just a little bit” of charge is a pain, so instead the delta symbol is used to show this.

δ+ = just a little bit of positive charge
δ- = just a little bit of negative charge

This can also happen to just one part of a molecule. A good example is a hydroxyl group (OH). The oxygen pulls the electrons toward it, so that there is just a little bit (δ) of charge on the oxygen and hydrogen atoms.

Molecules with hydroxyl groups are polar. Look at glucose - it has loads of hydroxyl groups; this is what makes it a polar molecule. This is important for how it behaves in water, but before we get to that, let’s look at how charged atoms/molecules are different:

Second step: What’s the Difference between Polar and Charged Molecules?

Polar

A polar molecule has no overall charge. The charge of its positive nuclei exactly cancel out the charge of its negative electrons.

The charges are just unevenly distributed, giving a little bit (δ) of positive charge to one atom, and slight negative charge to another atom.

In biology, you’ll normally find it’s a hydrogen atom that has had its electrons yanked away and is now carrying a little bit of positive charge.

Charged

Now look at this. These atoms are not sharing a cloud of electrons - the big one has gone all-in and taken the whole lot for itself.

No shared electron cloud means there is no covalent bond.

No covalent bond means they are no longer a single molecule, but rather two separate atoms … well, except that they’re not even atoms any more …

The atoms no longer just have just a little bit (δ) of charge. The one on the left has lost an entire electron’s worth of charge. Losing negative charge means that overall it is now (properly, not just a little bit) positively charged.

The one on the right has a whole electron’s worth of negative charge more than it needs to cancel out its positive nuclues. It is now (properly) negatively charged.

Because they are (properly!) charged, we no longer call them atoms. Instead they are ions.

Water experiences this sort of electron-theft.

Sometimes it exists as the polar H20 molecule, but sometimes its oxygen gets even more greedy and the molecule dissociates into H+ (a hydrogen ion, aka proton), and OH- (a hydroxyl ion).

This dissociation, and the reforming of H20, is happening all the time in normal liquid water.

Note that the ions each have an overall charge, unlike the polar water molecule where the small charges cancel out.

Bigger Molecules

Atoms that are negatively charged due to having extra electrons, or that are positively charged because they lack electrons, often occur in large molecules too.

Where positive charges are found, it helps to think about this as a positively-charged H+ having been added to the molcule.

Here’s an amine group. It’s just part of a larger molecule, which goes off the edge of the image.

It can exist either as —NH2, or it can add on a proton (H+) to become —NH3+.

In living organisms, there are plenty of available protons (remember how water dissociates?). So amine groups like this usually exist as the charged version.

This is not a polar group, it is charged. (Ignore the shape of the electron cloud for this one, the important thing is that there is an overall charge of +1 because of that extra proton).

Electrostatic Interactions

So. Polar molecules are uncharged overall but have just a little bit (δ) of charge in various places. While charged molecules have a big whack of charge due to having lost an electron or having gained a proton. Why is this difference so important?

It’s to do with how polar and charged molecules interact with their environments. It’s not the same.

Hydrogen bonds

Some polar molecules, like DNA, proteins and water, can form hydrogen bonds between the atoms that have the unevenly distributed charges. These are a special type of weak bond.

Water LOVES making hydrogen bonds - this is why it can hold itself together into a droplet.

Notice in the picture that the water molecules remain separate and can still move around. It doesn’t take much to pull a single hydrogen bond apart. Which is why water can still be poured and stirred around with no trouble.

Water is a polar, hydrogen-bonding molecule, and this explains its properties as a solvent. Molecules like glucose can dissolve in water because they are similarly polar and able to make hydrogen bonds.

Hydrogen bonds are also really important in understanding DNA and protein structures.

These molecules hydrogen-bond to themselves. Each individual bond is weak, but multiple repeating bonds work together to hold the structure into shape.

Protein secondary structures are held together by hydrogen bonds.

The image here shows hydrogen bonds between Guanine (G) and Cytosine (C) in DNA. The hydrogen bonds are shown as dotted lines.

To get a feeling for the strength of hydrogen bonds, think about what happens if you spill water on a book, close it, and let it dry. You know how the pages stick together? This is because hydrogen bonds have formed between the pressed-together pages. When you peel them apart, you are pulling these hydrogen bonds apart.

Dissolving ions

Charged ions like Cl-, Na+ and K+ can’t form hydrogen bonds, but they can still dissolve in water because they can form favourable electrostatic interactions with the water molecules.

This diagram shows salt (NaCl) dissolved in water.

Hydrogen bonds are in yellow. And electrostatic interactions between the charged ions and the polar water molecules are shown in green.

See how the water molecules organise around the ions to provide the opposite charge to that presented by the ion.

Non-polar molecules like lipids cannot form electrostatic interactions with water molecules. And so for this reason, non-polar molecules do not dissolve in water. If you could somehow spread a bunch of non-polar molecule through a glass of water, this would cause all sorts of problems because the water molecules next to the non-polar molecules would be unable to satisfy their charges. Water prefers to hydrogen bond to itself, and it would do so, squeezing the the non-polar molecules out to cluster together in undissolved lumps.

Whisk up a teaspoon of oil in a glass of water and watch - you can see this happening. The oil ends up as a separate layer on the surface. Or get a small glass of oil and carefully put a drop of water on top; the water will ball itself up, hydrogen-bonding to itself and minimising the amount of contact it needs to make with the oil.

This is why membranes don’t dissolve in the cytoplasm. The water molecules would much rather hang out with other water molecules where they can make all those lovely hydrogen bonds. Non-polar molecules are called hydrophobic, or “water-hating”, but to be honest that’s a bit unfair because really it’s the water is excluding them, rather than the other way around.

This also means that non-polar molecules can’t act as solvents for polar molecules or charged ions. The reason being the same: they can’t offer any way to satisfy the polar/charged molecules’ hankering for favourable electrostatic interactions. This is why ions (Na+, K+, H+ etc) cannot dissolve into, and move through, membranes. Which is absolutely vital to understand if you want to make sense of how neurons, mitochondria, and chloroplasts function (and many other things in biology besides).

Ionic bonds

Charged molecules have ‘proper’ charges. They interact more strongly through electrostatic interactions to form ionic bonds.

Here is a positively charged amine group (NH3+) forming an ionic bond with a negatively charged hydroxyl group (OH-).

They are not sharing an electron cloud, so this is not a covalent bond.

Maybe these charged groups are both parts of the same protein (ie from different R groups). If so, this interaction may be important in defining the protein’s tertiary structure.

Or maybe it’s an interaction between an enzyme and its substrate?

Ionic bonds are really important for controlling what binds with what - and what doesn’t. Negatively charged groups will repel other negative charges. And positive will repel positive. This prevents incorrect structures forming.

In summary:

Polar molecules are charge-balanced overall but have unevenly distributed electrons. This gives them a little bit ( δ ) of a negative charge on one atom, and a little bit ( δ ) of positive charge on another. In biology, these weak charges often form hydrogen bonds, or favourable electrostatic interactions with ions.

Charged molecules have an overall charge. They have at leat one full unit of charge on at least one atom. (A unit of charge being equal to the magnitude of one electron). These stronger charges can form ionic bonds with each other.

This article was written by Dr Jenny Shipway

AQA 3.1 biological molecules - 10 good practice questions on carbohydrates

3.1.2

Can you

• Draw the formation and hydrolysis of a glycosidic bond

• Name the 3 disaccharides and their components

• Explain why polysaccharides are good storage molecules ?

• Explain why are branched polysaccharides good ?

• Explain how are the properties of cellulose explained by the structure ?

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