Homology
Modeling Part-I
- assigned 10/5/11, due
10/19/11
You are to make a homology model (aka comparative model) of the human
enzyme Neutral Cholesterol Ester Hydrolase 1 (NCEH1) using the Swiss
Model server. The NCEH1 enzyme
has the NCBI accession code: Q6PIU2 or gi: 74737782
Websites visited in class
Swiss
Model - http://swissmodel.expasy.org/
NCBI PubMed -
http://www.ncbi.nlm.nih.gov/sites/entrez/
DeepView -
http://spdbv.vital-it.ch/
DeepView -
http://www.usm.maine.edu/~rhodes/SPVTut/index.html
PyMol - http://pymol.org/
Protein Data
Bank - www.pdb.org
Principles
of Protein Structure, Comparative Protein Modeling and Visualization
ExPASy
(http://us.expasy.org/)
CLUSTALW (http://www.ebi.ac.uk/clustalw/) - a program that
generates multi-sequence alignments in several formats
BOXSHADE
(http://www.ch.embnet.org/software/BOX_form.html) - takes output from
Clustalw and makes nice figure
you need for this assignment.
Complete
the 5 parts below to be turned in by our 10/19/11 class
1) Explain your choice of templates used
for
the modeling assignment.
In your answer make sure to make a convincing argument of why you chose
the templates you did. Also, pick at least one template which has
an active site ligand for the figure to be made in part-2.
2) Make a figure using the program PyMol that shows
a cartoon of your final "best" NCEH1 model. Draw the active
site Ser, His, Asp and active site ligands as ball and stick in the
figure. Submit to me the figure as a png file and insert a small
picture of this in your questions writeup to make it pretty.
3) Prepare a multi- protein sequence
alignment of your choice
of templates aligned with the target sequence. You could use the
programs ClustalW/Boxshade (demonstrated in class) or other programs of
your choosing. In addition to turning in your final sequence
alignments,
you should use this approach to help make decisions of what templates
to
include (part 1).
4) Send me (bahnson@udel.edu) an e-mail,
which includes
your best human NCEH1 model aligned with each of the templates you used
to
make
the homology model. This file should be a pdb format
file. When you receive your results back, open up the *.pdb
file in
Deep View to inspect file.
5) Sometimes, homology models that are
constructured from several
templates versus a homology model that is made from only the best
template
can give complementary information. Is that the case for your
homology
modeling of human NCEH1? Incorporate information derived from
parts
1-3 above, to answer the question posed here.
Explain.
6) If you were going to use a homology model
to help
solve a
crystal structure of human NCEH1 by molecular replacement.
Which homology model from part-5 would you use and why?
Also, would
you make any changes to the homology model in order to use it as a
molecular
replacement search model? Describe the changes you will make and
explain why.
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