Tuesday, March 18, 2008

Are You as Smart as a Third Year University Student? Q7

 
Question 1
Question 2
Question 3
Question 4
Question 5
Question 6
Choose the INCORRECT statement about protein folding.

a) protein folding is a cooperative phenomenon
b) the energy of the final folded protein is at the bottom of a free energy well
c) most proteins fold extremely rapidly
d) folding is an enthalpy-driven reaction (ΔH)
e) protein folding can be assisted by molecular chaperones


15 comments :

  1. Are You as Smart as a Third Year University Student? Q7

    This phrasing is irritating, as well as being inaccurate.

    These questions have nothing to do with being "smart." They look at whether you've been educated in the narrow discipline under consideration. Nothing more, nothing less.

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  2. It's a joke based on the popular TV program "Are You as Smart as a Fifth Grader."

    Lighten up.

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  3. Ah, well ... if your standard of excellence is a silly joke based on a silly TV program, who am I to interfere??

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  4. I find these statement either too vague ("most proteins fold extremely rapidly": how fast is extremely rapidly, by what standards?) or too precise ("folding is an enthalpy-driven reaction (ΔH)": always, or just sometimes?) to be clearly correct or incorrect. The most serious problem of vagueness comes in (b): "the energy of the final folded protein is at the bottom of a free energy well". What is "a" free energy well? Do mean the global minimum or will a local one do? If the former, how can we possibly know? If the latter, it's true, but only in the most trivial sense that absolutely any species that has a finite lifetime is at a lower energy level than all neighbouring states.

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  5. athel says,

    I find these statement either too vague ("most proteins fold extremely rapidly": how fast is extremely rapidly, by what standards?) or too precise ("folding is an enthalpy-driven reaction (ΔH)": always, or just sometimes?) to be clearly correct or incorrect.

    Here's how I explain it to my students.

    Biology is a messy subject with very few precise, inviolate rules. What we do in biology is create generalities or concepts that apply to most phenomena. It's important to learn and understand these general concepts. In class, I will always point out the exceptions but I will also try and explain why they are exceptions.

    When it comes time to write an exam we have several choices of format. I could ask simple fact questions like how many amino acid residues are there in sperm whale myoglobin.

    It's very easy to make up such questions but what purpose does it serve?

    On the other hand, I could ask questions that are based on understanding concepts and ideas. But there's a problem with those types of questions. Most of my students are very smart and most of them have been very successful at adopting a "student lawyer" mentality towards exam questions. If they can demonstrate that a question is the least bit ambiguous then they can get it eliminated. This is a highly successful strategy if you have selected the wrong answer.

    I tell my students that this won't work in my course. Students are told that many questions will examine general principles and it's not possible to phrase these questions in a way that eliminates all possible objections from the lawyers. There's simply not enough space on the exam for all the fine print.

    When faced with a question like to one above, students are supposed to select the answer that applies to typical molecules even though they may know of an exception or two.

    In this particular case, there is an obvious choice that is clearly not a general concept or principle of protein folding and that's the one they have to pick.

    I want my students to learn how science really works.

    Athel, are you having trouble identifying the incorrect statement? Do you want me to tell you the correct answer?

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  6. I'm going to say d) since protein folding is mostly driven by hydrophobic collapse, not enthalpy. Is that the right answer?

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  7. My point was that an unclear question has no right answer. However, as you challenge me, and I don't want to be like Jonathan Wells, I'll say what I think you wanted: (d). Nonetheless, if a student answered (b) and made some sensible comments about energy lanscapes I wouldn't regard it as wrong. (c) might just escape being condsidered wrong if accompanied by evidence of knowledge of likely rates.

    (a) is true;
    (b) is trivially true in the weak sense; I would guess that it's also true in the strong sense;
    (c) is true if you define "extremely rapidly" in a reasonable way;
    (d) is usually untrue, but I wouldn't feel confident that it is is never true;
    (e) is true.

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  8. I say C, based on rule 3 of my guide to improving your score on multiple guess tests.

    Rule 3 states that it's more difficult to state something correctly then it is to state something incorrectly, so short answers tend to wrong.

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  9. Choice (d) is clearly incorrect. Protein folding is an entropy-driven reaction not an enthalpy-driven reaction.

    Any scientist who said that protein folding is driven by enthalpic change would be considered ignorant of the field.

    Any student who ignores the obvious incorrect statement and picks another answer is demonstrating the he/she doesn't understand protein folding. The fact that they might make up nitpicky excuses for not recognizing the obvious is not going to get them a mark on this question.

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  10. I've got to say b. The wording implies that the structure must have the configuration which is at the global minimum when this need not necessarily be the case. The configuration need only be at a local minimum in the energy surface, provided that the energy barrier to other minima is sufficiently great over normal variations in temperature.

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  11. anonymous says,

    I've got to say b. The wording implies that the structure must have the configuration which is at the global minimum when this need not necessarily be the case.

    So, you think "d" is correct?

    You wouldn't get any marks in my course. Choice "b" is correct as a generality and it's generalities (concepts) that we try to understand in my classes. My students know about exceptions and, hopefully, they know that every important concept in biochemistry has exceptions. If I'm doing my job correctly, my students have move beyond nitpicking about exceptions.

    Apparently, you haven't. :-)

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  12. Choice (d) is clearly incorrect. Protein folding is an entropy-driven reaction not an enthalpy-driven reaction.

    Any scientist who said that protein folding is driven by enthalpic change would be considered ignorant of the field

    It is a pity you are being so dogmatic about this, and ignoring Einstein's dictum that everything should be made as simple as possible, but not simpler.

    You might want to have a look at Fig. 8 of Ken Dill's article in Biochemistry 29, 7133-7155 (1990), where you will see that the enthalpy of folding is not necessarily unfavourable, and not necessarily insignificant compared with the entropic effect. I assume you would not characterize him (and others that he cites, like Privalov, Gill, Tanford, etc.) as "ignorant of the field".

    The whole business is not as simple as you want to make it.

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  13. athel says,

    You might want to have a look at Fig. 8 of Ken Dill's article in Biochemistry 29, 7133-7155 (1990), where you will see that the enthalpy of folding is not necessarily unfavourable, and not necessarily insignificant compared with the entropic effect. I assume you would not characterize him (and others that he cites, like Privalov, Gill, Tanford, etc.) as "ignorant of the field".

    Nobody says that the enthalpic change is unfavorable. Nobody says that it is insignificant for all proteins.

    When you say that a given type of reaction is entropy-driven you are not saying that the enthalpy change is always unfavorable.

    The whole business is not as simple as you want to make it.

    The goal of teaching biochemistry to undergraduates is to give them basic concepts that they can use to understand fundamental biochemical processes.

    This does not mean that you ignore the exceptions. This does not mean that you teach dogma. Quite the contrary - at least in my classes.

    However, once you have established that protein folding, in general, is an entropy-driven process because of the hydrophobicity of the core residues, then that's the concept that you examine on the tests.

    I sounds to me like your way of teaching focuses too much on the exceptions and not enough on the concepts. That's too bad.

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  14. I think we're talking past one another here, and I doubt whether anyone else is still listening.

    I'll just comment on a couple of your last points. You say:

    Nobody says that the enthalpic change is unfavorable. Nobody says that it is insignificant for all proteins.

    When you say that a given type of reaction is entropy-driven you are not saying that the enthalpy change is always unfavorable.

    Well maybe not, but I don't suppose I'm alone in thinking that you're implying this. (If anyone out there is still following this, what do you think? Is Larry right, or am I? Not about the science, where I don't think there is any real disagreement, but about the likely meaning readers will attach to his words.)

    You also say:

    I sounds to me like your way of teaching focuses too much on the exceptions and not enough on the concepts. That's too bad.

    I hope you don't really think that. If you do, I think you're in a minority, as my books on kinetics have more often been criticicized (as long ago as 1976, by Freddie Gutfreund in TiBS if I remember rightly) for being too much focussed on principles and not enough on messy details.

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