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Download Jmol-14.29.29-binary.zip

Uncompress the zip file

Double-click on Jmol.jar in the uncompressed directory

 

Download Molecular_modeling1_pdb_files.zip and uncompress

 

File --> Console to get command line.

Commands to be typed in the console window will be listed in Courier.

 

Open files by going to File menu, then Open (File --> Open)

                         

Right-Click (PC) or Control-click (Mac) to get pop-up menu.

Go to Style in the pop-up.

Menu commands will be listed in Helvetica

Style --> Scheme --> Ball and Stick

 

In the image window, figure out how to zoom in and out, and how to rotate the molecule. You should zoom and rotate ALL the molecules you examine after each display change.

 

Oleic acid

 

Go to File menu, then Open (File --> Open)

Select oleic_acid.pdb from the uncompressed Molecular_modeling1_pdb_files directory

 

In the image window, figure out how to zoom in and out, and how to rotate the molecule. You should zoom and rotate ALL the molecules you examine after each display change.

 

Click on any atom. In the Console window you should see something like:

C5 #5 1.404 -3.432 -0.95900005

            C5 = atom name

            1.404 -3.432 -0.95900005 = x,y,z coordinates in Å           

 

Find atoms O20 and C19

Display --> Measurements on (checked)

 

Double click on O20 and move the pointer to C19. The distance should appear.

 

1. How does this distance compare to you experimental estimate of oleic acid size?

 

Helical peptide alpha1

 

File --> Open alpha1.pdb

 

In the console:

spacefill

spacefill off

Style --> Scheme --> Ball and Stick

ribbon

ribbon 200

ribbon only

ribbon 50

ribbon off

select all

Style --> Scheme --> Ball and Stick

backbone only

backbone 50

 

Now select only the Ca carbons in the backbone

select *.CA

Style --> Scheme --> Ball and Stick

backbone 50

 

Rotate to look down the helix.

 

1. How many amino acids per helical turn?

 

Find the first CA atom and click on it. What amino acid is it? Do for the entire structure.

 

2. What is the sequence in the canonical N-terminal to C-terminal order?

 

restrict backbone

Style --> Scheme --> Ball and Stick

ribbon 50

 

Display the backbone hydrogen bonds

hbonds calculate

 

Notice that the first 4 amides are not hydrogen bonded, and carbonyls 8,9,10 not hydrogen bonded. This gives the N-terminal end of the helix a partial + charge and the C-terminal end a partial - charge. This results in an overall electrical field dipole.

 

Immunoglobulin antibody binding protein G GB1

 

Protein G is a cell surface protein on Streptococcus bacteria that binds antibodies. It is made of multiple independently folded domains that each bind an antibody molecule. GB1 is one these domains. GB1 is perhaps the best studied protein molecule of all time.

 

File --> Open GB1.pdb

 

Style --> Scheme --> CPK Spacefill

The isolated red balls are water molecules. The protein structure was solved in water. While bulk water molecules diffuse rapidly, specific regions around proteins often have higher residence times for water molecules.

select water

color green

 

Now let's look at the backbone hydrogen bonding in the context of an entire protein.

delete water

restrict backbone

Style --> Scheme --> Ball and Stick

hbonds calculate

ribbon 100

 

The command show structure lists amino acid residues for each secondary structure element. While helicies are contiguous, beta sheets are made of strands. Each strand has a direction from N-terminus to C-terminus.

 

1. What strands form parallel (going in same direction) beta sheets with each other?

 

2. What strands form anti-parallel (going in opposite directions) with each other?

 

3. Is it necessary for strands that make up a beta sheet to be contiguous in sequence?

 

Now we will look at the distribution of different types of amino acid sidechains in a protein structure.

ribbons only

ribbon 400

hbonds off

 

First, the hydrophobic sidechains (ile, leu, val, phe, tyr, trp):

select sidechain and hydrophobic

Style --> Scheme --> Sticks

Style --> Scheme --> CPK Spacefill

 

Now, all the other non-hydrophobic sidechains:

restrict backbone

select sidechain and not hydrophobic

Style --> Scheme --> Sticks

Style --> Scheme --> CPK Spacefill

 

Now, re-examine the locations of hydrophobic sidechains:

restrict backbone

select sidechain and hydrophobic

Style --> Scheme --> Sticks

Style --> Scheme --> CPK Spacefill

 

4. What do you notice about the hydrophobic sidechains and how they are arranged in or on the protein? Why might this be?

 

GB1 complexed with IgG antibody

 

File --> Open GB1_IgG.pdb

 

Style --> Scheme --> CPK Spacefill

color chain

ribbons only

hbonds calculate

 

Zoom into the region between GB1 and antibody.

 

1. How do the backbones of GB1 and the antibody interact?

 

ribbons off; hbonds off

 

Select sidechains on GB1 (A) within 8.0 Å of antibody (G) and vice versa:

select within (8.0, :G) and :A and sidechain or within (8.0, :A) and not :A and sidechain

 

Reset the center of rotation to be at the GB1:antibody interface, and display the sidechains

View --> Define Center

Style --> Scheme --> Ball and Stick

hbonds calculate

Style --> Scheme --> CPK Spacefill

select backbone; ribbon 50; color chain

select within (8.0, :G) and :A and sidechain or within (8.0, :A) and not :A and sidechain

Style --> Scheme --> Ball and Stick

Style --> Scheme --> CPK Spacefill

 

2. What is the distribution of atoms at the molecular interface? How does this compare to the types of atoms found on the inside and outside of GB1 on its own?

 

3. What types of interactions appear to be driving association between protein G and antibody?

 

DNA

 

File --> Open DNA.pdb

Style --> Scheme --> CPK Spacefill

 

Rotate the molecule. You should note two grooves spiraling up.

 

1. Are these grooves equivalent?  

 

Style --> Scheme --> Cartoon

color chain

select bases

Style --> Scheme --> CPK Spacefill

 

Note how the bases are stacked on top of each other.

 

2. How does this compare to the protein core and protein complex you examined? 

 

Style --> Scheme --> Sticks

hbonds calculate

 

3. Without actually selecting any atoms or having memorized the structures of bases, you should be able to distinguish between adenine/thymine and guanine/cytosine base pairs. How?

 

hbonds off

select bases

Style --> Scheme --> CPK Spacefill

select backbone

hbonds off

 

Now examine linkages between nucleotide #6 and its neighbors #5 and #7

restrict 6:A

View --> Define Center

Style --> Scheme --> Ball and Stick

select backbone and 5:A or  backbone and 7:A

Style --> Scheme --> Sticks

 

We typically draw nucleotides such as #6 in two dimensions, with the base and sugar co-planar.

 

4. Describe the orientations of the ring planes of the base and sugar with respect to each other.

 

5. Bases are numbered from low to high. By clicking on the atoms, can you determine how this directionality is defined? Which sugar carbon is attached to the base? Which sugar carbon is attached to the preceding nucleotide? Which to the next nucleotide?

 

When you click on an atom, you should see something like this:

[DC]6:A.C2' #109 -6.258 46.192 -0.402

 

The [DC] refers to Deoxy-Cytosine (C). Similarly [DA] = A, [DG] = G, and [DT] = T

 

restrict :A

Style --> Scheme --> Ball and Stick

 

6. Write the DNA sequence in the canonical orientation.

 

7. What is the sequence of the other strand (in the canonical orientation)?

 

Maltose Binding Protein (MBP)

 

Maltose binding protein is used by E. coli to transport maltose in the periplasm.

 

File --> Open MBP_overlay.pdb

 

Examine maltose:

restrict mal

View --> Define Center

Style --> Scheme --> Ball and Stick

Style --> Scheme --> CPK Spacefill

 

Examine the maltose structure. In the unbound state, the polar atoms interact with polar water molecules. The protein must minimally compensate for these lost interactions in order to bind.

 

Examine the unbound protein:

restrict :A

restrict backbone

Style --> Scheme --> Trace

color magenta

select mal

Style --> Scheme --> CPK Spacefill

select within (8.0, mal ) and not mal and :A

Style --> Scheme --> Ball and Stick

Style --> Scheme --> CPK Spacefill

Style --> Scheme --> Ball and Stick

 

1. Are the maltose polar atoms all making interactions with the protein?

 

Let's see what happens to the protein structure upon binding to maltose.

restrict backbone

Style --> Scheme --> Trace

Color the unbound form (:A) magenta and the bound form (:B) cyan

select :A

color magenta

select :B

color cyan

select mal

Style --> Scheme --> CPK Spacefill

 

Note how one of the protein lobes bends down over the maltose in the bound (cyan) structure. This Venus flytrap conformational change is typical of the periplasmic binding protein superfamily. Other members include neurotransmitter receptors in eukaryotes (like us).

 

Now display the structure of the bound form of MBP:

restrict :B and backbone

Style --> Scheme --> Trace

color cyan

select mal

Style --> Scheme --> CPK Spacefill

 

Notice how the protein has two lobes, with the maltose ligand between them.

Zoom in and out to closely examine the ligand region.

 

Select only the protein atoms around the maltose

select within (8.0, mal ) and not mal and :B

Style --> Scheme --> Ball and Stick

Style --> Scheme --> CPK Spacefill

Style --> Scheme --> Ball and Stick

 

2. How does this differ from the unbound structure?

 

3. How does the protein compensate for these interactions that are lost by being sequestered from solvent water?

 

Polar atom interactions with water that are lost upon binding are compensated with equivalent interactions with protein atoms. However, in order to make binding more favorable than unbound, the protein must make additional interactions with the ligand, beyond what water can make.

 

4. What types of interactions might drive binding, such that the energy of the bound state is lower than the energy of the free state? In addition to the maltose structure, you might also want to look at the spatial distributions of sidechain and atom types in protein G you found earlier.

 

 

 

 

 

 

 

Navin Pokala, PhD
navin.pokala at nyit dot edu

Department of Biological and Chemical Sciences
New York Institute of Technology
Theobald Science Center, Room 423
​Old Westbury, NY 11568-8000
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