Simulation of Hemoglobin Function S. Scottlimmerman. COMPress. P.O. Box 102. Wentworth. NH 03282 Hardware: Apple II family Components: One disk with backup. Student Workbook Level and Subject: Biochemistry or physiolo9Y Cost $85.00
Revlew I Simulation of Hemoglobin Function is a program designed to help the average student better understand how oxygen is trausported by hemoglohin a t the molecular level. The effects of Con, pH, and 2,3-diphosp h o g l y c e r a t e ( 2 , 3 - D P G ) on oxygen transport are also demonstrated. The author, S. Scott Zimmerman, states in the accompanying workbook that "a major difference between the average chemistry or hiochemistry students and the top students, is that the average ones have difficulty visualizing molecular events". This program visumolecules colliding alizes the process of 0% and hinding to hemoglohin as a function of 0%PressUte. The simulation will then plot the percent of hemoglohin molecules saturated with 0 2 as a function of Oz pressure. The program can be used as a classroom demonstration to comolement lectures or i t can be w r d by individual students with the accompanying workbook as a laburatmy simulation.The program would be useful m a biochemistry or physiology course that explains h~rwO2 is ramied hy hemoglohm at the molecular level. If used as a labcmtors simulation, the availability of disks and workbooks to a large number of students may be a limiting factor. The 67-page workbook is an integral component of the simulation program. The workbook explains the student objectives and how it is to he used. A prior exposure to computers is not required t o utilize this program. A detailed description explains how ~
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to handle the disk, how t o insert the disk correctly, how to turn on the computer, and what to do if the program does not appear @ he working. The program was tested an a IIe hut is stated to work on a II+, IIe or an Apple compatible computer. The Main Menu provides a choice of General Direction, Hemoglobin Simulation, Myoglobin Simulation, and End. The keyboard commands are easy t o use and are introduced in the workbook as they are needed m the ~imulationA summary ofthe keyboardcommandiara pnwrd. ed on the last page of the workbook. A onepage introduction to hemoglobin structure and function is provided. Additional biochemistry textbook references and page numhers are listed for further information. The simulation follows the approach used by Luhert Stryer in Biochemistry to describe hemoglohin function. The workbook provides a set of detailed questions that guide the student through the entire program. Space is provided for writing answers and an answer key is provided a t theend of the workbook. Questions include asking the student to identify the molecule on the screen showing the four subunits (hemoglobin) and to identify the confornational state (Tor tense state as revealed by color). The student is asked to calculate the percent Oz delivered by bemoglobin after collecting the data in the simulation. Additional questions try to stimulate the student's thinking, for example, "Would a higher than normal level of cooperativity in hemoglobin be physiologically advantaemus?" ----The hasic simulation, used under a variety of different experimental conditions,
shows a single hemoglohin "molecule" being hit randomly by O2 molecules (small circles). As the 0 2 pressure is increased, more 0 2 molecules are observed colliding and hinding. When an Oz molecule binds t o a subunit in the T form, the blue subunit changes color to orange indicating the R (relaxed) confornation. The simulation measures the average number of binding sites occupied by that molecule over an extended oeriod of time. The oercent saturation is recorded constantly and a final value listed after the t m e rnterval is completed. On the other hand, mmt tett,oc,ks and instruct~m define percent saturation as the percent of hemoglobin active sites occupied by 0 2 in a large population of hemoglohin molecules a t agiven time point. The workbook provides a hvoothetical oroblem to show that both de. scription4 are equit,dlent. It is a critical poiur that may cause some confusion with students, but it can help rr#cstudrnt hrttrr clarify what is meant by the concept of percent saturation. The Oz pressure can be increased a t the keyboard in 10 torr intervals from 0 t o 100 tom.The simulation can he repeated a t each 0 9 .oressure t o calculate the oercent saturalion and the value plotred on rnegraph provided on the screen. The speed of rhr simw lation can be adjusted at the keyboard. The rate can be slowed or stopped to see the dynamics of the Oz molecules hitting, leaving, hinding, and being released. Six students in a jnniorlsenior level physiology course who tested the program complained
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Summary Ratings: catsgon Ease of Use: Subiect Matter Content
Pedsgcgic Value: Student Reaction:
Reviewer
Re~Iewer
I
Ii Above Average
Excellent Good God God
Average Goad Above Average
Reviewed In This Issue Reviewer
Computer Learning Packages S. Scott Zimmerman, Simulation of Hemoglobin Function David 6.Moss, Solution Equilibrium Problems D. L. Zellmerand 6.H. Gurnp, T h i n l a y e r Chromatography
A113
David Roll
Janina Kaars Don C a s s Marilee Murray D. B. Dahlberg Ernest Ferguson
A114
George 6. Kauffman
A118
All6
Books
G.Marco, 17.M. HoMingworth, and
W. Durham, Silent Spring
Revisited Continuing Series Titles of Interest Monographs
A118 A118 A119
Volume 65
Number 4
April 1986
A113
rhnt the time rrquirrd to complete all the rimulnr~onswas excessive. F:wn when the srmulntlons are dune at the highest spcrd, it takes one t o two minutes to obtain each saturation point. I t would be helpful to have the option of speeding up the simulation even more. The simulation progresses by exploring how the addition of COr. . a o H chanee. and 2,3-DPG cwwntration affect\ the 0, sarurationcurve The effect uf COun Or h:nding by hemoglobin is examined. The saturation curve for myoglobin is obtained and compared to that for hemoglobin. The different saturation curves are graphed in different colors and can be compared on the same graph. The concepts of eaoperativity and allosteric proteins are introduced by questions in the workbook. The proportional size of hemoglobin t o the 0 2 molecules is not realistic, but the workbook points this out and explains that moleit is necessary in order to make the 0% cules visible in the simulation. The symbols for hemoglobin are only diagrammatic; the polypeptide backbone and heme groups are not shown in detail. Such a picture of the four subunits and the accompanying change in quaternary structure upon Oz binding as revealed by the X-ray studies of Max Perutz would be a valuable teaching tool. The dynamics of three-dimensional structural changes are extremely difficult to visualize on the printed page. The resolution of the Aoole . . comouter makes that a difficult oroo. . u r l r ~ mAs . stated by the aurhor, the locusof this ~imulntioniz on f h r iunrrion of hrmoglubinnnd not on its strucrurc although thr concepts go hand in hand. As microcomputer resolution and memory increase, undergraduate students may soon have access to three-dimensional images of proteins a t the molecular level. The program can be recommended as a helpful supplement to understanding the concepts of cooperativity and allosteric proteins, although the above mentioned limitations should be kept in mind. The six students who completed the entire workbook spent between two and four hours a t the terminal. Students thought the program was helpful in understanding the concepts although they complained about the time required to complete the individual simulations. Whether the program is worth the price depends on what emphasis the instructor places on the comprehension of these concepts by students. David Roll Roberts Wesleyan College 2301 Westside Drive Rochester. NY 14624
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Review II Simulation ofHernoglobinFunction isan instructional package consisting of a single disk and a workbook. The author's objectives are t o provide students with a feeling for molecular dynamics by showing qualitatively and quantitatively the function of myoglohin and hemoglobin. He attempts to show the effects of certain small molecules and other species on hemoglobin function and provides the instructor with a package
A114
Journal
of Chemical Education
that can be used individually or as a classroom demonstration. Familiarity with the basics of hemoglobin and myoglobin structure and function prior to using the software is anticipated by the author. The program is easy to use with no obvious errors that could cause interruotions. There are clear dwctions for booting the disk and using the uurkbouk and nu prior knowledge of computer, is required. A glossary of all commands used to control the program is found in the workbook. In our department, the program was reviewed by four senior undergraduate biochemistry majors, a graduate student, a biochemistry professor whose primary research relates to hemoglobin function, and myself (the coordinator for our biochemistry undergraduate program).
tors might like to add this facility, hut the authur did nut dercrihe an easy way for the program to be modified. As no prior knowledge of computers is necessary, students had no trouble using the software without supervision. A colored model of the molecules is on the screen a t the same time as a graph; however, one student pointed out that the molecules should be in different shapes, along with different colors, so that black and white monitors can also be used. Most students enjoyed using the workbook, but some found the questions a little oversimplified. (i.e.; press a key, now write down what happens.) Beginning college students and high school students would probably not he insulted by such instructions. Our upper level undergraduates were.
Subject Matter The program is offered as a supplement t o more traditional methods of teaching and provides a list of references that may he useful. The software generates a screen that is divided into quadrants, with an animated eraohic deoictine hemoelobiu subunits and " active small molecules (such asoaveen.. CO,... and 60, Louncing around. Anofhrr arra of rhescrern provides agraph of prrcrnt saturation versus POP (or COX,or CO). The student can vary the gas concentration by using the keyboard and this willcreateaehange in the percent saturation and will also show a corresponding change in the number of gas molecules in the animation. In this particular case, as the number of oxygen molecules increases there is a resulting change in the hemoglobin T or Rstate. Students may also vary the rate of the reaction, which affects the resulting hemoglobin state. The function of hemoglobin in the presence of 2,3diphosphoglycerate (DPG) is also described. In summary, students can control the small molecules' concentrations and observe hrdh n llnegrnph %honingperrmt Jaruratam and the resulting alferts on hemutlf cmtnd pmvides glubin states. T h ~ iype i students with an opportunity to enhance their understanding of the functional relationship hetween hemoglobin and small molecules such as 02, COz, and CO. A few areas should be clarified in the procram. The removal of DPG modifies affinitv hut DPG remmnl d r m not r ~ d u r ecouperntrwry. although rhe pnwnm stnrea that it does. Also, this program demonstrates a model far hemoglobin, but there is no explanation for how this model is constructed. Underlying kinetic assumptions, choice of rate constants, etc. should be explained. Instructors and uooer level undereraduates shuuld be ahle tc, underitand suchan explnnatiw. This cwld have been g:wn in the u,orkbook, ii not in the suftware In drmunsrrnting rhe ~tarisricalmechanicsof rooprrarwny. the author uses the expwssi~n"Or rmpernrwity", which is nn tuntnmilior rrrm
The author should consider expanding the workbook to include more background about the "model" being demonstrated, emphasizing the fact that it is one model and explaining how this model is constructed. Paints related t o the reduction in cooperativity and percent cooperativity should be clarified. The oroeram .. itself could be impmved hy altering 11 sc,that aftergeneration of the fir51 line on the graph, lurrhrr iinrs could be getaerated mow quicklv.
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Summary This program has effectively combined the interactive nature of computer-assisted instruction with an animated graphic to demonstrate the dynamics of molecular interaction. Because the author has succeeded in his stated goals, it should be a valued instructional tool. althoueh the use of this program will he limited I
