'96 BC/BP 378
Week 1
Exploring molecules. You will look at the molecular building blocks of life. You will also explore the relationship between the stick drawing of molecules used in most textbooks and the actual 3-dimensional conformations of these molecules.
Author:
Susan Jean Johns
Welcome to BC/BP 378. In this course you will expand your understanding of the molecular nature of life by applying computing techniques to problems in molecular biology. These techniques will allow you to analyze both protein and nucleotide sequences and visualize their structures.
This first week's activities will center on a visual review of the molecular building blocks of life. You will run a series of demonstrations with a molecular modelling piece of software called MacroModel. After the first demonstration, each demo will require you to perform some function in order to finish out the topic being explored.
For this first week, do not worry about the mechanics of doing computing tasks. These functions: activating the computer in the lab, making connections to the platform housing the software to be used, and running the needed software, will be dealt with later in the course. Right now concentrate on visually exploring molecular biology.
To ensure that you get credit for your explorations, enter the following term at the terminal's $ prompt, signon. This will cause the following lines to be displayed on the screen.
Please enter your name into the computer to receive credit for your activities today. Instructions: Enter the first character of your first name followed by an underscore and then your last name as given in this example, s_johns Enter your name:
Do just what this text says. Enter your name as described above and press the ENTER key. It will probably take you two lab periods to complete this week's activities. Mark your progress in your exercise handout. When you come in next time, repeat this signon step, move on to the place you had marked and continue on with the exercise series.
The software you will be using, MacroModel, can be run in an automatic mode through the use of a log file. All the necessary log files to view the various aspects of molecular biology that we will review have been created and are named so that just entering the name of the topic will start the demo.
Before attempting to use MacroModel, there are some facts about the program you should be familiar with.
1) MacroModel is set up with a working display window surrounded on the bottom and right-hand side of the screen by a series of option buttons, and an area for program messages to the user (or user input window) at the top. Use the option buttons to communicate your wishes to the program. To activate a button, move the cursor (or cross-hair) to the button's location and press the spacebar. Cursor (or cross-hair) control on your machine is with the mouse. An activated option button is colored green. The message (or user input window) area either informs the you of the status of an option button with multiple selection possibilities, requests parameter input, or relates error messages.
The following is the initial screen of the MacroModel program.
When the program is started the initial screen shows this image with the INPUT and ORGANI buttons colored in green. The input of organic molecules is the default operating mode of the program upon startup.
2) There are two different types of option buttons, those which move the program to major function areas, and those which set the parameters for a given function. The major function buttons are located at the bottom of the screen and parameter buttons are on the right-hand side.
3) The default atom colors used by the program are: green for hydrogen and carbon, dark blue for nitrogen, pale green for phosphorous, red for oxygen and yellow for sulfur.
4) When the program is running on automatic, such as in the demos you will be doing, there is no real way to pause the program to let you study a structure.
A type of pause has been created by changing between the various operating modes of the program. You will notice at times while a demo is running that the image in the working window will remain the same while the buttons are changing. This pause allows you to study what is on the screen. The rate at which a demo runs depends on the number of users on the system. The greater the number of users, the slower the demo. You can expect that the demos will probably run slower than you would like them to. If things run too fast, press the left alt key together with the scroll lock to stop the screen. Pressing these keys again resumes the demo.
Section 1: overview demo
The first demo is an overview for the building blocks of molecular biology. You will be shown an image composed of a number of different molecules representing the various building blocks. The demo will then zero in on each one of these molecules in order, tell you what general type of building block the molecule represents and its name, and then give you some idea of the molecule's actual size.
To start the demo, enter the following term, overview. In the following instructions, terms given in bold text are to be entered on the keyboard followed by pressing the ENTER key.
$ overviewThe following text will appear on the screen.
**** MacroModel V3.0 ****
Copyright Columbia University 1990
All Rights Reserved
Initializing MMOD. Please stand by..
If desired, enter LOG or name of script file:
At this point enter the following term and press the ENTER key, overview.log . The program will then query you if this is a batch process or not with the following prompt.
Batch? (N?Y):
Respond with n for no. You will see information about the terminal that is expected by the program to be used for this demo displayed on the screen. The program will then bring up the initial screen that was shown earlier and start the automatic demo process.
If you see the following text on the screen, there is a problem with starting the program. Get help from your instructor.
Terminal options:
1. E&S PS3xx (PS)
2. Lundy 5481 (L4)
3. DEC VT241/340 (V2)
4. DEC VT100/VT640 (V1)
5. Tektronix 41xx (TK)
6. Pericom MGxxx (PE)
7. Mac/VersaTermPro (MV)
8. Mac/Tekalike (MT)
Enter terminal type:
The image on the screen is that of 6 molecules. There are five molecules
located in a pentagon around a central one. The middle one is a water
molecule. Each of these molecules will expand to fill the working window and
then the image will change to show the molecule's building block type and its
own compound name. After viewing this screen for a few moments to allow you
enough time to copy down the compound name, the molecule is returned to the
screen. Its image is adjusted down to fit in the central portion of the
working window. A Van der Waals surface is then drawn around the stick figure
originally shown. This is to give you a better idea of the molecule's actual
shape and size. A number of C's will appear on the screen marking the
overall dimensions of the molecule. Distances will be displayed to give you an
idea of the shown molecule's overall size in angstroms. After all 6 of the
molecules has been looked at, the demo will automatically stop. Record the
names of these six molecules in the space provided below.
_____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________
Section 2: water
Now, let's look in depth at the 6 building types shown in the overview. You will start with the one on water. Water is the solvent of carbon-based life. Its properties influence all molecular interactions in biological systems. It is not linear and therefore has an asymmetrical charge distribution. The oxygen nucleus with 8 protons attracts electrons more strongly than does the hydrogen nuclei. Thus the O-H bond is polar, with the oxygen atom bearing a partial negative charge and each of the hydrogen atoms a partial positive charge. This charge separation produces a permanent dipole whose negative end points to the oxygen, and whose positive end bisects the H-O-H bond.
Water with its polarity permits the permanent dipoles of the O-H bond to attract one another. Thus the slightly positive hydrogen of one water molecule attracts the slightly negative oxygen of another water molecule producing a dipole-dipole interaction known as a hydrogen bond. Hydrogen bonds are weak (only 4 kcal mol-1) when compared to covalent ones. Such bonds are most stable when the hydrogen and its two electronegative partners are linear, however deviations up to nearly 45 degrees still result in some level of hydrogen bonding.
The physical properties of water are governed by hydrogen bonding. In liquid water, each water molecule is hydrogen bonded to 3.4 other water molecules. Liquid water is an extensively hydrogen-bonded network of water molecules with the water molecules perpetually rearranging their bonding patterns. Ice has each water molecule hydrogen bonded to 4 other water molecules. The resulting crystal lattice is more open with fewer atoms per unit area, and is therefore less dense.
Water, with its ability to form hydrogen bonds and its polarity, interacts with solutes dispersed within it. Ionic substances are soluble because net attraction of the positive and negative ions for water is greater than that of the attractions of the oppositely charged ions for one another. Nonpolar substances are insoluble in water because the water-water interactions are stronger than the water-nonpolar substance interactions. The stronger water-water interactions cause the nonpolar substances to collect together and to be surrounded by the water molecules. This event is called the hydrophobic effect and the nonpolar substances are called hydrophobic or water hating. Those substances that readily dissolve in water are called hydrophillic or water loving.
To start this demo enter the term, water. You respond to the question about a script file with water.log and the one about doing a batch process with n. If you need help with this set of instructions, refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ water water.log n
The demo starts with the drawing of a single water molecule. This drawing is then converted into a realistic water molecule by going through the minimization process. You will notice that the ENERGY button is chosen, the MM2 button and then a Start button. The buttons on the right-hand side of the display then change and you see the terms Iter, Movt and kJ/mol at the top of this section of the screen. As the structure is minimized, numbers appear in rows of three in this area. They are reporting the status of the minimization process. When the numbers are replaced and the structure of water re-drawn, the image you have on the screen is that of a realistic energy minimized water molecule.
The size of the water structure is adjusted to just a small central portion of the screen. Colored dots appear around the stick drawing. A Van der Waals surface has just been placed around the molecule. This gives you a better idea of the actual shape of the molecule. The molecule will be re-sized again and the terminal will beep at you twice. At this point you take control of the program and go through the steps necessary to produce a stereo image of the water molecule. Ask your instructor for a stereo viewer to continue this process.
Move the cross-hair over to the STREO button. Press the spacebar to activate this button. Two images appear in the middle of the working window. Place the stereo viewer up against the terminal screen. Align the viewer so that the bottom is below the objects on the working window and the center section of the viewer is between the two images. It may be necessary to move the viewer back and forth a few times until the image snaps into focus.
After you have looked at the 3-D image, get out of the program by moving the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and exit the program.
Section 3: bases demo
The third demo is about nitrogenous bases. Nitrogenous bases are derivatives
of either purine or pyrimidine that, together with a sugar
(
-deoxyribose or ribose) and one or more phosphate groups, form
nucleotides.
Get into MacroModel and view the demo for nitrogenous bases Entering bases starts up the program. You respond to the question about a script file with bases.log and the one about doing a batch process with n. If you need help with this set of instructions, refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ bases bases.log n
The demo starts with its name, bases. It then moves on to show you the five possible bases used to form various possible nucleotides: adenine, cytosine, guanine, thymine, and uracil. The image on the screen has adenine and cytosine in the top row. Guanine and thymine are in the middle row and uracil is by itself at the bottom. Next a file is shown displaying the component parts of a nucleotide and the resulting nucleotide. The produced nucleotide expands to fill the working window and its dimensions are determined.
The demo moves on to show the growing of a DNA double stranded helix with the following sequence, GGGCATGG. Once grown, this given strand is colored aqua, its complement colored white. The starting nucleotide in the sequence is colored green so that you can find the start of the helical segment. The generated DNA segment is then rotated three times by 60 degrees to give you an idea of what such a helical DNA structure looks like from different angles.
Hydrogen bonding plays a large part in holding such a DNA structure together.
The hydrogen bonds for the structure are now determined. Record the number of
hydrogen bonds found below.
Number of hydrogen bonds: ____________________________________________________
The image is clipped to show only its middle and that section is rotated slightly to allow a closer look at the structure. Notice how the hydrogen bonds (which are shown in purple) go between the members of each strand as well as between the two strands.
DNA can assume three forms, A, B or normal, and Z. Each of these forms has slightly different helical shapes. The size of the grooves change with each form as does the view down the central axis. All three conformation side views are shown in one image. The three end views are shown in another. The A form of DNA is colored red and white in these images. The B or normal shape of DNA is dark blue and purple. Z DNA is aqua and yellow.
Proteins and other molecules can bind to DNA, forming complexes. Examples of
these complexes are shown next. The first is that of a small organic molecule
(orange) fitting into the minor groove of a DNA strand. This is a modelled
structure. The second is that of a protein binding to DNA. The structure
shown contains the minimum amount of information necessary to create such an
image. Only the phosphorous atoms are given for the DNA structure, while only
the 
-carbon atoms of the protein backbone are given for the protein.
The image is that of the catabolite gene activator protein interacting with
normal DNA and is from actual x-ray data. The final structure is that of a
carcinogen, 3,4-benzpyrene (shown in green) inserted within a DNA double
stranded helix. This is a theoretical model.
After the carcinogen image appears on the screen, the terminal will beep at
you. This is your signal to take over the control of the program. At this
point, use the mouse to move the cross-hair over to the HBOND button.
Press the spacebar. This will cause the color of this button to change to
green. As before in the demo, the number of found hydrogen bonds will be shown
in the user input window and purple lines will be drawn to show the location of
the actual bonds. Examine the effect of the carcinogen on the bonding
patterns. Record your observations below in the space provided.
_____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________
To exit the program and complete this section, move the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you.
Section 4: sugars demo
You have already seen that two sugars (-deoxyribose and ribose) are
used to form nucleotides. Sugars can form complex polymers. The simple sugar
glucose can be stored by living things in various ways to be used later as a
source of energy.
Animals store glucose as glycogen, a very large, highly branched polymer
connected mainly by -1,4-glycosidic bonds, but with branching provided
by -1,6 linkages. In glycogen, a -1,6 linkage occurs once in
every 10 units. Plants store glucose as starch. One form of starch is
unbranched (amylose which uses -1,4 linkages) and the other is
branched (amylopectin which has mainly -1,4 linkages but also some
-1,6 linkages) although not to the same extent as glycogen. In
amylopectin, -1,6 linkage occurs once in every thirty units. Yeast
and bacteria store glucose as dextran. Dextran uses -1,6 linkages
almost exclusively.
Sugars also form structural elements in the cell walls of bacteria and plants
and in the exoskeletons of arthropods. In these situations, the sugars are
linked by -1,4 linkages, thus forming long linear chains. Such chains
are capable of forming fibers of high tensile strength. In cellulose (the
structural element for bacteria and plants) the sugar used is glucose. In
chitin (the structural element of arthropods) the sugar is
N-acetylglucosamine.
Sugars can also be attached covalently to integral membrane proteins on their extracellular face. And many secreted proteins, such as antibodies and clotting factors, also contain sugar units. A large number of sugars are involved in the formation of these glycoproteins. Normally these sugar units are attached to the protein via a O-glycosidic bond to either a serine or a theronine, although sometimes the linkage is through a N-glycosidic bond with asparagine.
To start this demo enter the term, sugars. You respond to the question about a script file with sugars.log and the one about doing a batch process with n. If you need help with this set of instructions, refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ sugars sugars.log n
The demo starts with its name, sugars. It then shows you five of the many possible sugars used in forming carbohydrate compounds: glucose, sucrose, lactose, maltose and N-acetylglucosamine. In the displayed image, the glucose molecule is red, sucrose is white, lactose is yellow, maltose is orange and N-acetylglucosamine is shown in the default atom colors of the program. Three of these examples (sucrose, lactose, and maltose) point out the different linkages available to complex sugars. Sugar linkages are hard to tell apart from one another.
The demo then shows you the polymeric repeating units of cellulose and chitin, the two most abundant biopolymers on earth. Cellulose is made from glucose, while chitin is from N-acetylglucosamine. Notice how similar these two units are. The chitin unit has an acetylated amino group (nitrogen is colored blue) and this group slightly distorts the structure as compared to the original cellulose one.
Next an example of a glycoprotein is shown. The image on the screen is that of hemagglutinin from influenza virus. Only the backbone of the protein is shown. This is a very large protein, only one third of it is displayed on the screen. Because of its size, the image takes a long time to appear. The A chain is white, the B chain yellow and the small section of carbohydrate is red. There are also four individual sugar molecules included along the sides of the structure. These were left in default atom colors.
Again the terminal will beep at you. The cross-hair will be found by the STOP button. It is time to complete the demo, move the cross-hair to the Clip button. Press the spacebar. The Clip button will turn green. Now move the cross-hair over to a point on the working window that is just a little below the red carbohydrate section. Be sure to include some of the white structure as well. Press the spacebar. A red mark will appear on the image. Move the cross-hair over to a point on the working window that is above and to the right of the red carbohydrate region. Press the spacebar again. A second red mark appears. The working window then clears and the area that you marked off is expanded to fill the entire working window. Look closely at the red colored section of the image. Record below if you think that the carbohydrate section shown is branched or not.
Observation of the carbohydrate region: ______________________________________
To exit the program, move the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and the prompt will return.
Section 5: phosphates
There are a number of biological important acids and bases, however one of the most important of these is phosphoric acid. It appears in some ionic form in the cellular fluids of all organisms. A phosphate compound is the carrier of free energy in biological systems, adenosine triphosphate (ATP). ATP is an energy rich molecule because it contains two phosphoanhydride bonds. A large amount of energy is released when ATP is hydrolyzed into either ADP and orthophospate or AMP and pyrophosphate. ATP, ADP and AMP are inter convertible. Phosphates also form part of the backbone for DNA and RNA structures.
To start this demo enter the term, phosphates. Respond to the question about a script file with phosphates.log and the one about doing a batch process with n. If you need help with this, refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ phosphates phosphates.log n
After displaying the topic of the demo, the process shows you a phosphoric acid molecule. Next, ATP is displayed in the working window. The image that follows is that of ATP, ADP and AMP. ATP is on the left-hand side of the image and AMP on the right. Notice that they only differ from one another by the number of phosphate groups. An image is next displayed showing the location of the phosphate groups within a small section of DNA. One strand is green (5'-3' strand) the other white (3'-5'' strand). The phosphate groups are shown in aqua. The final image is that of two small DNA sections. The same coloring scheme is used here as in the previous image to denote the DNA strands. The first one is intact. The second one shows the results of a blunt end restriction enzyme cleaving the small chain.
After the two DNA sections appears on the screen, the terminal will beep for
you. This is your signal to take over the control of the program. Use the
mouse to move the cross-hair over to the H ADD button. Press the
spacebar slowly three times. This will activate the button and add
hydrogens to the two structures. Green lines will be added representing the
added hydrogens. Look closely at the second structure. How were the
additional hydrogens added to the cut ends of the original 5'-3' strand?
Record your observations below in the space provided.
_____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________
To get out of the program and complete this section, move the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and exit the program.
Section 6: lipids
Lipids are water-insoluble biomolecules that are highly soluble in organic solvents. They play a number of different biological functions. They serve as fuel molecules, signal molecules and as components for membranes. In this section, we will be looking at the role lipids play in biological membranes and therefore will be dealing with phospholipids, glycolipids, and the steroid cholesterol.
Biological membranes are diverse in structure and function, however they do have a number of common features:
1) They are sheet-like structures that form closed boundaries between compartments of different compositions.
2) Membranes are composed mainly of lipids and proteins. The function of the membrane is controlled by the nature of the proteins embedded into the lipid structure. Carbohydrates may be attached to the both the lipid or the protein component of the membrane.
3) Membrane lipids are relatively small molecules with one end of the molecule hydrophobic and the other hydrophillic. These lipids automatically form closed biomolecular sheets in the presence of water. For the lipids being looked at here, this means the formation of bilayers in which the hydrophillic ends of lipids form the surface of the bilayer and the hydrophobic ends form the inside of the structure.
4) Membranes are held together by non covalent forces and therefore are fluid structures. They can be considered two-dimensional solutions of oriented proteins and lipids.
Phospholipids:- These lipids are derived from either glycerol or sphingosine and consist of the alcohol backbone, two fatty acid chains and a phosphorylated alcohol. The fatty acid chains usually contain an even number of carbon atoms, typically between 14 and 24, with 16 and 18-carbon atoms fatty acids being the most common. On the next page is the generalized formula of a phospholipid.
Glycolipids:- Glycolipids are sugar-containing lipids. In animal cells, glycolipids are derived from sphingosine. Their sugar component may contain as many as seven branched sugar residues. A generalized formula for a glycolipid is shown below.
H H H | | | H3C-(CH2)12--C=C--C---C-CH2-O- sugar unit H | | HO N-H | O=C | fatty acid unit
Cholesterol:- This neutral lipid is present in eucaryotes but not in most procaryotes. Its only hydrophillic section is its hydroxyl group. In humans, cholesterol is the predominant steroid in the body and serves a number of different purposes. Cholesterol has the following formula.
Lipid bilayers are readily formed by phospholipids and glycolipids in aqueous solutions. Such bilayers are held together by reinforcing, noncovalent interactions. The bilayers are asymmetric and have definite inner and outer surfaces. Lipid bilayers are impermeable to ions and most polar molecules. Such bilayers form permeability barriers in which integral membrane proteins carry out the membrane functions. The thickness of a bilayer varies with its constituent lipids. The hydrocarbon core of plasma membranes is ~30 angstroms. However overall, most membranes are between 60 and 100 angstroms thick. Many integral membranes are ~75 angstroms and purple membranes ~45 angstroms.
Start this demo enter the term, lipids. Respond to the question about a script file with lipids.log and the one about doing a batch process with n. If you need any help refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ lipids lipids.log n
The lipid demo starts with its name, lipids. It then shows an example of a phospholipid molecule and then an glycolipid molecule. The structure of cholesterol comes up next. A lipid bilayer is displayed. Notice the two rows of opposing molecules. The generic bilayer shown is composed entirely of 1-palmitoyl-2-palmitoyl-phosphatidyl ethanolamine. This is not typical of a membrane bilayer, which usually is composed of a number of different lipids. A Van der Waals surface is drawn around the bilayer components.
Now finish off this demo. Two C's will have been shown on the right hand side of the working window and the ADist button will be green. Use the cross-hair to select the top C and press the spacebar. The terminal will beep at you. Now move the cross-hair to the bottom C. Again the terminal will beep, this time it will show the distance between the two Cs as well. Record this distance in the space provided below:
bilayer width: ______________________________________________________________
How does this compare with the lipid bilayer thickness given earlier?
Get out of the program by moving the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and exit the program.
Section 7: amino acids
Amino acids are the building blocks from which proteins are made. Some amino acids are charged and therefore hydrophillic. Others are hydrophillic, but not charged. Still others are hydrophobic. Since individual amino acids have the properties of charge and hydrophilicity, so do their resulting proteins.
The individual amino acids in a protein are linked together by a peptide bond.
Peptide bonds are themselves very rigid, however the protein backbone has
complete freedom of rotation around its -carbon atoms thus allowing
for the creation of various conformations for amino acid residues and the
folding of the backbone.
The folding of the protein backbone into periodic structures creates secondary structural elements. These structural elements are known as helixes, sheets and turns. Hydrogen bonding between the N-H and C=O groups of the protein backbone helps stabilize these secondary structural elements.
Proteins come in a variety of sizes, from the very small to the very large. They may contain substrate units or have disulfide bridges. Different protein families have different folding patterns. Some proteins contain only helical secondary structural elements, others only sheets. Some contain a mixture of both helixes and sheets. A few contain only turns.
Start this demo enter the term, proteins. Respond to the question about a script file with proteins.log and the one about doing a batch process with n. If you need any help refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ proteins proteins.log n
After the intro screen showing the topic to be looked at, the demo displays the 20 standard amino acids. These are shown in alphabetical order starting in the upper left and working their way across and down the screen. These are shown in turn colored by their charge. Basic amino acids are dark blue, acidic are red and neutral ones yellow. Next the amino acids are colored by their hydrophobic nature. This time, hydrophillic amino acids that are charged are dark blue, uncharged hydrophillic ones are aqua and hydrophobic ones yellow.
After looking at individual amino acids' characteristics, the demo shows you the formation of peptide bonds between three amino acids. The image starts with each amino acid on the screen in their original state. A peptide bond forms by the splitting off of water from the two amino acids forming the bond. The amino acid contributing the carbonyl group loses a hydroxyl group and the amine group contributor loses a hydrogen atom off the amine. The demo shows the bonds between these atoms being broken and then the isolated atoms disappearing. A bond is then drawn between the C=O and the NH groups. This bond is hardly realistic and so it is then normalized to meet standard parameters for such a bond. This process is repeated to form the second peptide bond.
Proteins have secondary structure. They fold into helixes, sheets and turns. An example of each secondary structural element is looked at. Their backbones have been colored white to make them easier to recognize. Hydrogen bonding patterns are determined so that you will be able to see the types of hydrogen bonds characteristic of each structural element. Helixes form hydrogen bonds between backbone CO and the NH groups that are 4 residues along in the linear sequence. Sheets form hydrogen bonds between the CO and NH groups of the separate sheet sections. Turns form a hydrogen bond between backbone CO and the NH group that is 3 residues along in the linear sequence.
Next a series of protein structures are shown that are color coded based on their secondary structure. Helixes are red, sheets yellow and turns aqua. The undefined regions of the proteins or their random sections are white. The proteins displayed in this way are insulin-like growth factor 2, calmodulin, and lysozyme.
Proteins come in all levels of complexity. Some are relatively small, others very large. The next screen shows two examples of this variation in size. On the screen is melittin which is 26 residues long and photosynthetic reaction center which is contains 4 chains and a total or 1191 residues and 15 substrate groups. The image on the screen only shows the backbone atoms of the respective structures. After the image has been on the screen for a while, two Cs will appear along side each of these molecules depicting their size in the y direction. These distances will be determined to give you an idea of just how different these molecules are in size.
Finally an image of the protein cytochrome c will appear on the screen. It will have a heme group included in the structure that is colored purple. It is now your turn to work with a protein and finish off this demo. After the beep, select the Rchrg button. Respond with w followed by pressing the ENTER key to the next question. This will have the amino acid residues color coded and not the heme group. The cytochrome c molecule will now be re-drawn in colors reflecting the individual amino acid residues charge - blue for basic, red for acidic and yellow for neutral. Notice where the charged residues appear to be. Select the RHpb button to see the molecule displayed to reflect its individual hydrophobic nature. Again, respond with w followed by pressing the ENTER key to the next question. This will result in amino acid residues being color coded but not the heme group. Dark blue residues are charged hydrophillic ones, aqua ones are uncharged hydrophillic ones and yellow residues are hydrophobic. Again, notice where the hydrophillic residues appear to be in the molecule. Record below in the space provided, where you believe most of these residues are located (on the surface or the interior of the molecule).
location of charged or hydrophillic residues: ______________________________
Get out of the program by moving the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and exit the program.
Section 8: familiar molecules (optional)
This extra credit section explores the structural conformations of familiar molecules from your environment. Some of these materials you ingest, others you inhale, some are naturally produced in your body, while still others are the result of humans attempting to control the world and mucking things up.
Start this demo enter the term, familiar. Respond to the question about a script file with familiar.log and the one about doing a batch process with n. If you need any help refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ familiar familiar.log n
The topic familiar molecules is shown in the working window. The demo shows you the molecular structures of aspirin, caffeine, and chocolate. The active psychogenic ingredient in marijuana is shown next, followed by that for morphine and the theoretical structure of leu-enkephalin, a naturally produced pain killer. The structures of DDE (the decomposition product of DDT) and TCDD (the highly toxic impurity in dioxan) are given next. The final image is that for a structural comparison of chocolate (orange) and caffeine (white).
After the beeps, you take over. The two structures on the screen are very
similar. To see just how similar, perform a superpositioning of the two
molecules one upon the other. In the message box is the notice, Select atom
pairs. Look closely at the atoms of the six member rings in each molecule.
Move the cursor over to one of the atoms of this ring on the orange molecule
and press the space bar. After the terminal beeps at you, move the cursor over
to the corresponding atom on the white molecule and press the space bar again.
Again a beep, but this time an orange dashed line is drawn between the two
atoms. Repeat this process two more times until a total of three lines connect
the two molecules. Now select the RigSp button. After the data is
worked with, you will be asked Plot superimposition (Y/N), respond with
y. The white molecule will be redrawn on the orange one. Record your
observations below and on the next page as to just how similar these two
molecules are.
_____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________ _____________________________________________________________________________
Get out of the program by moving the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and exit the program.
Section 9: sex (optional)
This section explores some of the molecules relating to sex. Hormones control the process of puberty changing our bodies into their adult forms. The act of sexual intercourse also triggers the release of additional hormones that change our behavior as well. This demo looks at some of these hormones that influence our lives.
Start this demo enter the term, sex. Respond to the question about a script file with sex.log and the one about doing a batch process with n. If you need any help refer to the instructions given for the overview demo. If you are having problems, ask your instructor for help.
$ sex sex.log n
The topic sex is shown in the working window. The demo shows you the molecular structures of both the male (testosterone) and female (estradiol) sex hormones. After intercourse the level of the hormone, vasopressin is increased in the male. This causes him to become more aggressive, territorial, and protective of his sex partner. Likewise, after intercourse the level of oxytocin increases in the female. She becomes more attached to her sex partner. At least this is the case with voles. Both vasopressin and oxytocin have other functions, but they appear to play a role in pair bonding. The final image is for a structural comparison of vasopressin (orange) and oxytocin (yellow).
After the beep, you take over. The two structures on the screen are similar.
To see just how similar, perform a superpositioning of the two molecules.
Since the two molecules are much larger than the last ones you did a
superpositioning on, these have the tack points color coded to help you. Move
the cursor over to the red atom of the orange molecule. Press the space bar
and have the terminal beep. Now move the cursor over to the red atom on the
yellow molecule and press the space bar again. An orange dashed line will
appear between the two red atoms. Repeat this process with the purple colored
atoms and the blue ones. Always start with the specially colored atom on the
orange molecule and then go the same colored one on the yellow molecule. When
the three orange dashed lines are drawn, select the RigSP button and
have the results plotted on the screen. This time the molecules are too large
to see anything when both of them are overlaid on only a small portion of the
screen. Move the cursor to select Scale from the top of the right hand
side of the screen. After the Scale button is green, move the cursor to the
lower left hand corner of the working window, press the space bar. After the
small red cross appears, move the cursor to the upper right hand corner of the
working window, press the space bar. A second red cross will appear and then
the entire image will be redrawn to fill the working window area. Look at
these molecules closely. Record how similar they are below.
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Get out of the program by moving the cross-hair to the STOP button and press the spacebar. Respond with y to the two questions that the program asks you and exit the program.
Section 10: Finishing up
With your demos completed, fill out the report form on the following pages and turn it into your lab instructor before the end of your second lab period for the week. Use the data collected during the running of demos to complete the form.
Week 1 Lab Report
Name: ______________________________________________________________________ Lab section: Monday/Wednesday __________ or Tuesday/Thursday __________ 1) How many hydrogen bonds were found in the DNA helical section displayed in the bases demo? 2) How did the insertion of the carcinogen molecule distort the DNA helix? 3) How do the ATP, ADP and AMP molecular structures differ from one another? 4) What was the width of the studied bilayer structure in the lipids demo? How well does this compare with the other bilayer thickness that were given? 5) Where do the charged or hydrophillic amino acid residues tend to appear in a protein structure? optional questions: familiar molecules question:How similar are the structures of chocolate and caffeine? sex questions: 1) What are the molecules of vasopressin and oxytocin composed of and how do they differ from one another? 2) Just how different from one another are the two different sets of sex hormones that you looked at? Speculate on the nature of molecular differences and function.