Molecules of Life Overview All living organisms are composed primarily of carbohydrates, lipids, proteins, nucleic acids, and water. There are many similarities and differences among these different types of molecules. Your task is to identify some of the similarities and differences through use of molecular visualization. For this exercise you will use a web browser to visualize the structures using Jmol applets.

Jmol Fundamentals The Jmol applet allows the user to manipulate 3D images of molecules in a variety of ways. For example, you can change the size of the molecule, change the view of the molecule (e.g., you can view the molecule as a ball-and-stick model, a wireframe model, a space-filling model, a cartoon which displays various structures, and several additional model types), change the color of atoms or groups of atoms, identify atoms and groups of atoms, and rotate molecules. Jmol requires a Java enabled browser. Internet Explorer on PCs, and Safari and Firefox on Macintosh computers work. The following is a brief list of options for manipulating molecules: Display information about the molecular components: Display atom identity for carbohydrates, lipids, and inorganic molecules - Place cursor over atom. The single-letter code for the atom name (see below) will be displayed. Display atom and amino acid identity for proteins - Place cursor over atom. The threeletter code identifying the amino acid and the single-letter code for the atom name (see below) will be displayed. Display atom and nucleotide identity for DNA - The single-letter code identifying the individual nucleotide is displayed in brackets ([A] - adenine, [T] - thymine, [G] guanine, [C] - cytosine) followed by additional numbers and letters and then the singleletter code for the atom (see below). Display a menu of commands - Place the cursor over Jmol and depress the mouse button. Rotate molecule in the X,Y plane - Place the cursor over the molecule, depress the mouse button, and move the mouse. Rotate molecule around a central axis - Place the cursor over the molecule, depress the mouse button while depressing the option key, and move the mouse from side to side. Zoom - Place the cursor over the molecule, depress the mouse button while depressing the shift key, and move the mouse towards or away from you. Most molecules will display as Ball & Stick models with CPK coloring. The balls represent the atoms and the sticks represent the bonds. The following list includes the CPK colors for the more common atoms. Grey - carbon (C) White - hydrogen (H) 1 of 6

Red - oxygen (O) Blue - nitrogen (N) Yellow - sulfur (S) Orange - phosphorus (P) Some molecules have water molecules associated with them. These excess water molecules typically display only the red oxygen atoms unbonded to any atom. To hide water, go to the menu (depress mouse button over Jmol), choose Select, then Hetero, and then Water. Return to the Select menu and choose Invert Selection. Return to the Select menu and choose Display Selected Only. Many large molecules (e.g., proteins and nucleic acids) don't display hydrogens. Please remember that all organic molecules have hydrogen bonded to free valence electrons of carbon, oxygen, and nitrogen even though they are not displayed. Go to the Life's Molecules web site and begin your tour of the molecules that make us living organisms. Prepare answers to the following questions.

Dead or Alive? View molecules from non-living sources (Ethane, Octane, and Cyclobutane) and living sources (Glucose, Cholesterol, Arachidonic Acid, Oxytocin, CHE*Y Signal Transduction Protein, ATP, and B-DNA) and answer questions 1-4 for all of the above molecules and question 5 for Ethane, Octane, Cyclobutane, Glucose, Cholesterol, Arachidonic Acid, Oxytocin, and ATP only. 1. 2. 3. 4.

What atoms are present in this molecule? What pairs of atoms form bonds in this molecule? (i.e., C-C, C-H, etc.) How many bonds can each type of atom form? What is the overall structure of this molecule? (e.g., single straight linear chain, single bent linear chain, more than one linear chain, one ring, more than one ring, etc.) 5. What is the chemical formula for this molecule? (e.g., count the number of each of the atoms to determine the chemical formula - C5H10O5) 6. Oxytocin only question: What are the names of the nine amino acids present in this molecule? (Render the Structure as a Backbone and then Color the Backbone by Scheme Amino.) 7. CHE*Y Signal Transduction Protein only questions: a. How many alpha helices are present in this molecule? (To view alpha helices and beta sheets change the display: Render Structures Cartoon, Color Cartoon by Scheme Secondary Structure.) b. How many beta sheets are present in this molecule? 8. What generalizations can you make about the differences between the molecules found in living organisms and other types of molecules? 9. Which three atoms are most common in biological molecules? (Remember that H atoms are not generally displayed in proteins and nucleic acids even though they are present.) 10. Which of these three common atoms makes the most bonds? 11. What role does carbon play in biological molecules? 12. What properties of carbon allow it to play this role? 13. Which of these molecules is the largest? How do you know? 14. Which group of molecules (carbohydrates, lipids, DNA, or proteins) has the most complex structure? Why?

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Structural Complexity You have just completed a brief tour of the simple structures (e.g., chains, chains with branches, rings, and rings with branches) that comprise organic molecules. You have also determined that it is the versatility of the carbon atom that produces these different structures. Now let's look at higher levels of structural complexity. Two common secondary structures found in proteins are alpha helices and beta sheets, and of course the double helix is found in DNA. Select the Alpha Helix and then change the view by choosing the following from the menu: Render Structures Cartoon Color Cartoon (choose a color) Reload the molecule (refresh the browser window) Render Scheme Sticks Select Protein Backbone Select Display Selected Only Render Hydrogen Bonds On Begin with the first amino acid (ALA 1) and move through the protein to answer the following questions. 15. Which atoms participate in hydrogen bonding in this protein? 16. List the different amino acid pairs that form hydrogen bonds in this molecule. 17. Is there a pattern to the position of the hydrogen bonds? If so, what is it? Select the Beta Sheet and then change the view by choosing the following from the menu: Render Structures Cartoon Color Cartoon (choose a color) Reload the molecule (refresh the browser window) Render Scheme Sticks Select Protein Backbone Select Display Selected Only Render Hydrogen Bonds On Answer the following questions: 18. Which atoms participate in hydrogen bonding in this protein? 19. List the different amino acid pairs that form hydrogen bonds in this molecule. 20. Is there a pattern to the position of the hydrogen bonds? If so, what is it? Select B-DNA and change the view by choosing the following from the drop-down menu: Render Scheme Sticks Select Nucleic Bases Select Display Selected Only Render Hydrogen Bonds On Select Nucleic AT pairs Reload the molecule (refresh the browser window)

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Render Scheme Sticks Select Nucleic Bases Select Display Selected Only Render Hydrogen Bonds On Select Nucleic GC pairs Answer the following questions: 21. Which atoms participate in hydrogen bonding in this protein? 22. List the different nucleotide pairs that form hydrogen bonds in this molecule, and record the number of hydrogen bonds that each nucleotide pair participates in. 23. Is there a pattern to the position of the hydrogen bonds? If so, what is it? General Questions 24. What role do hydrogen bonds play in proteins? 25. Why do proteins have such complex structures? (i.e., Is there a relationship between structural complexity and functional complexity?) 26. What role do hydrogen bonds play in DNA?

So Why Can't You Mix Oil and Water? For this investigation you will need a little background information. Atoms consist of a positively charged nucleus surrounded by a cloud of negatively charged electrons. Under many conditions there are equal numbers of positive and negative charges so the atom is electrically neutral. In molecules, atoms share their electrons to form chemical bonds. The shared electrons move around both nuclei to maintain the bond. Often the electrons are shared equally, maintaining electrical neutrality over the whole molecule. However, some nuclei attract electrons more strongly than others. (Chemists call this "electronegativity".) In these cases the electrons spend more of their time at the strongly attracting nucleus than at the weakly attracting nucleus. This leads to a charge imbalance on the molecule. The region that contains electrons more of the time becomes slightly negative and the region that is electron poor becomes slightly positive. This kind of molecule is said to be "polar". In biological molecules, polarity is created by the relative number of oxygen atoms; the greater the relative number of oxygen atoms, the greater the polarity. Oxygen has a strongly attractive nucleus that is able to pull electrons away from hydrogen and carbon. View Water, Octane, Stearic Acid, Cholesterol, and Glucose and answer the following questions. 27. What is the chemical formula of the molecule? 28. Would you predict that there is polarity in the molecule? Explain why or why not. Polarity, or lack of polarity, determines how molecules interact with each other. One way to think about this is to consider how magnets behave. They have magnetic polarity indicated by a north and a south pole. You probably remember how these poles interact: North and south will attract but if you try to push two north poles or two south poles together, they will resist. Electrical polarity works in the same way: positively and negatively charged regions will attract while like charges repel.

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Based on your answer to the water question above, predict how 3 or 4 water molecules would interact. (Sketch your answer.) One final rule, significantly simplified for our purposes, is that interactions between charged regions of polar molecules are favored as are interactions between nonpolar molecules. In effect, polar molecules that can interact will do so and will "push aside" nonpolar molecules. 29. Which of the molecules that you have examined so far would you expect to mix with water? 30. From the model, can you identify regions of that molecule that might be polar? (What are they? Why do you think that they are polar?) 31. Which of the molecules that you have examined so far would you expect not to mix with water? 32. From the model, can you identify regions of that molecule that might be polar? Nonpolar? (What are they? Why do you think that they are polar or nonpolar?) 33. At a molecular level, what happens when you mix oil and water?

Details, Details, Details Open the file with glucose, fructose, and galactose. 34. 35. 36. 37.

What is the chemical formula for glucose? What is the chemical formula for fructose? What is the chemical formula for galactose? How do these three molecules differ?

Open the file with sucrose and lactose. 38. 39. 40. 41.

What is the chemical formula for sucrose? What is the chemical formula for lactose? How do these two molecules differ? Most humans are born with the ability to digest both sucrose and lactose. A few are unable to digest lactose from birth while many others lose the ability to digest it later in life. Their ability to digest sucrose remains unchanged. Why? (Hint: Think about how enzymes function. e.g., What features of a substrate do enzymes recognize?)

Open the cellulose file. 42. Describe the structure of this molecule. 43. Identify the components (not atoms) of this molecule. Compare DNA nucleotides (dAMP, dTMP, dGMP, dCMP) with RNA nucleotides (AMP, UMP, GMP, CMP). 44. How does the sugar in DNA nucleotides differ from the sugar in RNA nucleotides?

Amino Acid Code G

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Glycine

Gly

P

Proline

Pro

A

Alanine

Ala

V

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L

Leucine

Leu

I

Isoleucine

Ile

M

Methionine

Met

C

F

Phenylalanine

Phe

Y

Tyrosine

Tyr

W

Tryptophan

Trp

H

K

Lysine

Lys

R

Arginine

Arg

Q

Glutamine

Gln

N

E

Glutamic Acid

Glu

D

Aspartic Acid

Asp

S

Serine

Ser

T