Basic Principles of Chemistry that Drive Protein Folding - Part 1
This Jmol Exploration was created using the Jmol Exploration Webpage Creator from the MSOE Center for BioMolecular Modeling.
Proteins are large molecules that are synthesized in the polar, watery environment of the cell. They are made by joining amino acids together in a particular sequence. Because each of the 20 amino acids is different in shape and chemical property, proteins fold up into different 3-dimensional shapes following basic principles of chemistry.
Globin Proteins such as hemoglobin safely carry oxygen in the blood.
Hemoglobin PDB ID: 1a3nInsulin Proteins help regulate sugar in the bloodstream.
Insulin PDB ID: 2hiuGreen Fluorescent Proteins create bioluminescence in animals like jellyfish.
green fluorescent protein (GFP) PDB ID: 1enbPrimary Structure is the sequence of amino acids in a protein.
Secondary Strutctures are the alpha helices and beta sheets in a protein.
Tertiary Structure is the overall shape of a folded protein.
Quaternary Strutcture is the assembly of multiple protein chains into a single complex.
For a more thorough introduction to the four layers of protein structure (primary, secondary, tertiary and quaternary), visit the Protein Structure tutorial.
The Amino Acid Starter Kit from 3D Molecular Designs introduces the basic principles of chemistry that drive protein folding. This Jmol tutorial will allow you to determine how accurately a real protein, ß-globin, reflects these concepts in its final, folded structure.
Click on the button below to see the ß-globin protein shown to the right in spacefill format, in which each atom is represented by a sphere the diameter of the atom's electron cloud. The protein has been colored with the CPK color scheme, meaning each type of element will have a unique color assigned to it.
Note that the Jmol display to the right is fully interactive and can be rotated by clicking and dragging with your mouse!
The first prinicple of chemistry that drives protein folding suggests that hydrophobic amino acids should be buried inside the protein where they can hide away from the water that surrounds the protein.
Simultaneously, hydrophillic (polar and charged) amino acids should be on the surface of the folded protein where they are exposed to and can interact with water.
To make it easier to visualize where the hydrophobic and hydrophilic amino acids are on the ß-globin protein, click the buttons below to apply a more visually useful color scheme. in this scheme, hydrophobic residues are colored yellow and hydrophilic residues are colored red.
Hemoglobin Hydrophobic and Hydrophilic PDB ID: 1a3nThe CPK colored molecule that is buried in the ß-globin is known as the heme group. The orange colored atom in its center is iron (Fe) and binds to oxygen gas (O2).
What is the function of the ß-globin protein?
Notice that proteins are a lot like students (and most adults!) in that they don't follow all of the rules all of the time. Can you see examples of hydrophobic amino acids that are exposed on the surface of ß-globin?
To get a better look at the inside of the protein, use the button below to slab the protein. Slabbing a molecule in a 3-dimensional Jmol display visually cuts it in half, making the half of it visually closest to invisible.
Hemoglobin Slabbed PDB ID: 1a3nNote that you can change the slab depth by holding the Ctrl and Shift keys and drag up and down using the left mouse button.
How well do you think ß-globin follows this first priciple of chemistry that drives protein folding: that the hydrophobic amino acids should be buried and the hydrophillic (polar and charged) amino acids should be exposed on the surface of the protein?
Although there are a few hydrophobic amino acids that are exposed on the surface, the central core of the protein, seen in the slabbed view, is entirely hydrophobic. So hemoglobin follows this principle of chemistry fairly well!
The second principle of chemistry that drives protein folding suggests that charged amino acids will be on the surface of a globular protein and that positively-charged amino acidss will often be paired with negatively-charged amino acids.
Click the button listed below to adjust the way ß-globin is displayed in the Jmol window to the right. Then use the interactive Jmol display to determine how well this second principle is followed in ß-globin.
Hemoglobin Positive and Negative Residues PDB ID: 1a3nAre the charged amino acids exposed on the surface of ß-globin?
yes
sometimes
no
Charged amino acids - both positively-charged and negatively-charged - are mostly exposed on the outer surface of the ß-globin protein.
Rotate this final image to examine closely how the positively-charged and negatively-charged amino acids are positioned in this protein.
Are the negatively-charged amino acids paired up with positively-charged amino acids?
yes
sometimes
no
There are three pairs of positively-charged and negatively-charged amino acids on the surface of this protein. The rest of the charged amino acids do not make pairs.
Proteins like ß-globin are large molecules that exists in the polar, watery environment of the cell.
The 3-dimensional shape of ß-globin is determined by basic principles of chemistry that drive protein folding:
While both of these basic principles of chemistry are reflected in the final folded shape of ß-globin, there are exceptions. Often the exceptions are important and suggest something about the function of the protein.
In this section, you can explore other proteins to see if they follow the basic principles of chemistry in the way they fold. For each protein, a paragraph briefly describes its function, including a link to the Molecule of the Month article about that protein. Several buttons allow you to explore the structure:Backbone shows the overall shape of the protein - amino acid sidechains are not displayed.Spacefill shows all atoms in the protein colored in cpk.Slab shows the protein in spacefill with hydrophobic residues colored yellow and hydrophilic residues in red. The top 50% of the protein is cut off so you can see 'inside'.Charged shows a backbone model with positive and negative charged amino acid sidechains displayed. See if you can find any positive-negative interactions!
Insulin is a peptide hormone that signals liver and muscle cells to take up glucose after you have eaten. Type 1 diabetes is due to an inability to make insulin. In type 2 diabetes, cells are unable to 'hear' the insulin signal and respond.Insulin Molecule of the Month
Insulin Backbone PDB ID: 2hiuTrypsin is an important digestive enzyme that helps to break down proteins you eat to recycle amino acids into YOUR proteins. Trypsin cuts proteins into smaller bits at either a lysine or arginine residue.Trypsin Molecule of the Month
Trypsin Backbone PDB ID: 2ptnGreen fluorescent protein (GFP) is the protein that causes jellyfish to glow green. Scientists use this protein as a research tool. If they insert the GFP DNA in front of a protein of interest in an embryo, they can determine which cells in the body produce the protein they are studying because these cells express GFP and glow green. You might have seen images of green glowing mice or fish!GFP Molecule of the Month
GFP Backbone PDB ID: 1embIon channels, such as the potassium channel, are membrane proteins that allow specific ions to move across the cell membrane. The concentration of potassium ions inside and outside the cell plays an important role in transmitting nerve signals.Potassium Channel Molecule of the Month
Potassium Channel PDB ID: 1bl8Antibodies are an important part of our immune system. When you are infected with a pathogen, such as a bacterium or a virus, your immune response includes a mechanism of chopping invader proteins into little pieces (called antigens). These antigens are presented (introduced) to immune cells that make proteins called antibodies that can bind to a specific antigen. So each time you are exposed to a different antigen, your body makes new antibodies against that antigen. Vaccines are typically a way of exposing your body to antigens (without making you sick) so you can create new antibodies to protect you if you are exposed to the pathogen.Antibodies Molecule of the Month
Antibody Backbone PDB ID: 1igt