Example questions
"Test-exam" for 2007-2008
Seminar 1: Homology modelling
- Explain the relation between Darwin's theory and `homology modelling`.
- Homology modelling of protein structures normally proceeds along a series of
distict steps. List those steps and describe the major problems encoutered
with each step, and possible solutions to those problems.
- Think of three very different scientific problems that can be (partly) solved
using a protein structure or homology model.
- What are the two major concepts behind homology modelling?
Seminar 2: Structure quality
- Explain the main conceptual differences between X-ray and NMR as structure solution techniques.
And explain how these differences express themselves in the kinds of errors you find in the structures.
- Take a look at the PDBREPORT entry for 1cbn and 1crn.
List for both structures the three errors that worry you most. Which of the two structures would you
use as a homology modelling template? (At the exam you will get these reports on paper).
- List the conceptual steps in the determination of a protein structure using X-ray techniques. Indicate
for each of the three till five major steps how they contribute to the errors in the final structure.
- Discuss the differences between structures determined by X-ray and structures solved using NMR in terms
of the information you can obtain from them.
- If I correct one error in an X-ray structure, the whole structure becomes better. If I correct one error
in an NMR structure, only the area around the correction improves. Which conceptual difference between
X-ray based and NMR based structure solution causes this effect?
Seminar 3: Force Fields
- Give 5 examples of force fields used in science and five used outside science. Write for each in (much) less than 100
words the essentials of the concept (which data is used for training/testing; which rules are used; which parameters
need optimization).
- Given 1000 proteins P with known structures (and thus with known secondary structures). Write the steps needed to
design a force field that can be used to predict the secondary structure of proteins for which the structure
is not known. Give the essential formulas. List the computer programs needed and describe (briefly) what each
program must do. Which force field parameters need to be optimized to get the best results?
Seminar 4: What sequences tell us
- What is a fundamental difference between the analysis of correlated mutations in multiple
sequence alignments and the determination of residues that determine the shape of phylogenetic trees?
- Think of a few easy to measure/determine whole-protein characteristics that can be analyzed on
a per-residue basis using correlation techniques?
- In the seminar we discussed Entropy and Variability as two measures of the result of evolutionary
pressure. 1) Explain the difference between these two measures. 2) Think of at least one more
measure that looks like Entropy and/or Variability in that it tells you something about the
evolutionary pressure, but is fundamentally different (from E and V).
Seminar 5: Drug docking
- Describe the stages in the whole drug-docking process, and indicate where in silico drug-docking contributes.
- Estimate how much money can be earned extra if in silico drug docking can make the total development
time of a (in the future well-selling) medicine one week shorter.
- Which are the main problems one encounters when doing in silico drug docking.
- Describe at least four types of mobility that can be observed in proteins. (With different types I mean either a very
different time-scale, or a very different amplitude). If any of these types of mobility is important for drug
docking indicate why, and indicate at least one solution (either existing or new) to deal with this mobility in
in silico drug docking.
real Exam 2007-2008
This is a long list of questions. You need to answer6 question. Don't make more than 6 questions because
I subtract points for every error. So if you make more than 6
questions you cannot gain points, but you can only make more errors. Choose your questions carefully.
Question thirteen is special. You cannot loose many points when you do it wrong. But you can gain points when
you do it right! So if you have any ideas about question 13, it is worth taking that one.
Use the space left free underneath the question for your answer. If you need more space than that, you are definitely
too wordy. Most questions can be answered with 100, at most 200, words.
Please write readable. I will have to read 40 times 6 (and that is 280) answers. That is rather much work... If I
cannot read something I will save myself time by simply assuming that it is wrong....
- Homology modeling of protein structures normally proceeds along a series of distinct steps. List those steps and
describe the major problems encountered with each step, and possible solutions to those problems.
- What are the two major concepts behind homology modeling? I.e. which two, rather fundamental rules
cause that homology modeling is at all possible?
- Explain the main conceptual differences between X-ray and NMR as structure solution techniques. And
explain how these differences express themselves in the kinds of errors you find in the structures.
- We presently know the X-ray structure of some 50 proteins that pass the membrane using a bundle of helices.
How would you proceed writing a computer program that uses this (still small) set of data to write a program
to predict where trans-membrane helices occur in proteins for which the sequence is known, but not the
structure? Hint, the answer needs to include a simple force field.
- How can I predict which cysteines are bridged and which cysteines are not bridged from a multiple sequence alignment?
- Which are the main problems one encounters when doing /in silico/ drug docking? Now
take one of these problems and write a small proposal about the research you would do to solve that problem.
- Describe (with or without formulas, I don't care) the forces we use in most of today's Molecular
Dynamics (MD) software packages. These forces are the main part of the force field of these methods.
Ten years from now, computers will be 50 times faster. That allows us to calculate more things. Which
terms would you add to the force field so that we do more precise MD calculations in 2018 than we do
today. (Hint computers will be 50 times faster, not 50 thousand times).
- One day in the near future you will be a bioinformatician. Think of three questions that a medical doctor
might one day ask you, and indicate what softwares will be needed to answer those questions.
- Think of a series of scientific applications that can be done better when PDB files are accessible that
contain fewer errors than is presently the case.
- Can you think of a force field that can be used in organic chemistry. And one for astronomy? And one for
surface chemistry? Describe for each of these three force field the question you want to answer, the data
you need, and in a few words what the data and the algorithm will look like.
- Which concepts underly the idea that we can extract functional information from a multiple sequence alignment?
- Mention four significantly different steps in drug docking. Mention for each of these steps the main
problems and give some hints how we can overcome those problems.
- The seminars (Homology modeling, Structure quality, Force Fields, What sequences tell us, Drug docking, MD,
Application), the practical session (looking at protein structures), and the interviews, all are related to
each other. Do you see the red thread through these elements? How are the topics of the seminars related? How
do the topics need each other?
2008-2009 exam with video answers
The following table holds a short intro and one video per exam question (2 videos for the question regarding what the topics
have in common)
2010-2011 exam
The exam as docx file
- And the last few questions were:
- What are correlated mutations, and what happens in evolution that causes that we
can find them in multiple sequence alignments?
- How do you find bridged cysteines or calcium-binding residues in a multiple sequence alignment
- What is a multiple sequence alignment?
Give three non-trivial (and significantly different) biological questions that can be answered using a multiple sequence alignment.
- It might be a bit far-fetched, but sequence alignments are using a force-field. Which is that force-field? And what does it look like?
2013-2014 exam
The exam with (very short) answers.