Astellas Protein Modeling

prunelimitΔίκτυα και Επικοινωνίες

23 Οκτ 2013 (πριν από 3 χρόνια και 8 μήνες)

96 εμφανίσεις

Fall 2012

1

Astellas
Protein Modeling
Challenge

February 28, 2013

SIZE RESTRICTION NEW THIS YEAR

The finished model must fit into a box that is
44cm x 28cm x 21cm.

You may bring additional display materials with
you on the day of the competition.

Fall 2012

2

Location


Registration in SAC Ballroom A


Testing and Model Building on the 3
rd

floor of
the SAC


The Astellas Scientists want to
CHAT
with
your students so after the exam and modeling
building the students will display their
prebuilt models in SAC Ballroom A. They will
stand by their model ready to discuss and
explain it. This interlude will not be judged.


Your students may bring handouts or whatever to
show during the chat session

Fall 2012

3

Fall 2012

4

Joan Kiely, Stony Brook University


joan.kiely@stonybrook.edu


Debbie
Pelio
, Stony Brook University


cesame@stonybrook.edu


http://www.stonybrook.edu/cesame


Linda
Padwa
, Stony Brook University

Kristen La Magna,
Stony Brook University


Shannon Colton, Ph.D., Technical Advisor


Milwaukee School of Engineering

http://cbm.msoe.edu/

Fall 2012

5


To compete successfully in the Protein
Modeling Challenge, you will:



Meet and get to know
the estrogen
receptor and why it is an important target
for rational drug design


Build models that illustrate what you know
about the receptor, steroid hormone
signaling, and breast cancer.


Become
a maven of protein structure


Enhance
your computer skills with
Jmol

Protein Modeling Challenge

Useful Web sites


Protein Data Bank
http://www.pdb.org/pdb/home/home.do


Center for Biomolecular Modeling
http://cbm.msoe.edu/


Tutorial for using
jmol

note that the Protein
Challenge is not exactly like the Science
Olympiad so the tutorial is not an exact match


CBM
jmol

resources
http://cbm.msoe.edu/stupro/smart/resources
.html
, you can download
jmol

from this site.

Fall 2012

6

Fall 2012

7

Web
-
Based Resources


This powerpoint presentation will serve as an interactive resource
for your team to gain the knowledge they need to be successful in
the Protein Modeling Challenge



You will find links distributed throughout this presentation,
indicated by the
blue underlined text



Follow these links to the appropriate sources



Good luck and have fun!


The following links will serve as tools
to help you learn the basic information
needed to be successful in this
challenge. Please follow these links:

Basic
Introduction to Protein Structure and
Modeling


http://cbm.msoe.edu/teachRes/index.html

go to the
bottom of the page for links


http://cbm.msoe.edu/stupro/so/index.html





Protein Databank Molecule of the
Month, THE ESTROGEN RECEPTOR,


The category Infrastructure and Communication,
subcatagory

communication with hormones has
useful background
articles.
http
://
www.pdb.org
/
pdb
/101/
structural
_view_of_biology.do?c
=
Infrastructure_and_Com
munication

Fall 2012

8

Protein Structure
Resources

Fall 2012

9


Proteins are macromolecules


Amino acids are the basic building blocks of proteins


Working as a team, make an amino acid

Protein Structure




Nitrogen



Amino Group



Carboxyl
Group




Alpha
-
Carbon




Sidechain (R
-
Group)





is
your amino acid L or D form?

Fall 2012

10











D
-
Alanine



L
-
Alanine



Fall 2012

11

Amino Acids Have Unique
Chemical Characteristics


Each amino acid has the same “backbone” structure, but has
different chemical groups (R groups or sidechains) attached



Working with another team, construct an amino acid and a
dipeptide with a molymod kit



NH
2
-
CH
-
COOH


R

Fall 2012

12


A linear chain of amino acids is the
protein “primary” structure



A chain of amino acids will
spontaneously form stable
“secondary structures”, ie: beta
-
sheet or alpha
-
helix



Hydrogen bonds may stabilize these
structures


Science researchers would like to
understand what controls this
folding.


http://fold.it/portal/


Proteins Have Secondary
Structure

Alpha Helix

Beta
-
sheet

Fall 2012

13


Protein folding is due to the behavior of different chemical
groups on amino acids in an aqueous environment



Proteins Fold Into a Tertiary
Structure

Structural Biologists and Computer Scientists are collaborating
improve our ability to predict protein structure and better
understand
MOTIFS and DOMAINS
in proteins

You can explore amino acid
sidechain

chemistry and protein
structure through the game and
programs at:


Fold It:
http://fold.it/portal/


or

Rosetta@Home

http://boinc.bakerlab.org/


Fall 2012

14


Proteins spontaneously fold into a specific three dimensional
“tertiary” structure that governs a protein’s function

Proteins Fold Into a Tertiary
Structure

Fall 2012

15

Protein Data Bank


The 3
-
dimensional structure of proteins is often determined
by x
-
ray diffraction or NMR analysis



PDB file lists the X, Y, Z coordinates for each atom in a
protein



Protein Data Bank

http://www.pdb.org/pdb/home/home.do



PDB Molecule of the Month

features the structure and
function of a different protein

each month

http://www.pdb.org/pdb/static.do?p=education_discussion/
molecule_of_the_month/alphabetical_list.html

Fall 2012

16

Molecule of the Month (MOM)


A monthly PDB feature written by David
Goodsell


http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_m
onth/alphabetical_list.html



Features a specific molecule



Describes protein function



Relates structure with
function






This figure is a science
-
artist’s
interpretation of a tyrosine kinase
receptor (it is not the estrogen
receptor)

The image is based on biochemical,
genetic and structural (NMR and
crystallography) data. Notice how
many types of scientist were
involved.

Fall 2012

17

Jmol


Jmol

is a computer visualization software that displays data
from a PDB file as a “3D” image of the molecule on the
computer screen


Jmol

is Java
-
based and will work on most
computers


http://cbm.msoe.edu/teachRes/jmol/index.html


Be sure that you know how to use the downloaded version before the
day of the competition. Also be sure that you can use the console
display.


http://jmol.sourceforge.net/

has
jmol

for downloading and
userguides
.


http://
bioportal.weizmann.ac.il/oca
-
docs/fgij/index.htm


Note that this version of
jmol

is easier to use but is not the interface
the students will use at the competition.


Your students should practice using the console and a
downloaded version!


We will be using version 13.0


Fall 2012

18

Exploring Protein Structure

with Jmol


Jmol

allows you to identify elements of protein structure



Helix (magenta)



Sheet (yellow)



N
-
terminus (blue)



C
-
terminus (red)



Amino acid
sidechains

(CPK)



Alpha
-
carbon backbone model
format



Spacefill

to get a sense of the volume



Surface view to give a holistic view of the protein

Fall 2012

19

Mini
-
Toober Models (cont.)


Mark location of structures on Mini
-
Toober



Fold Mini
-
Toober into a 3D model representing protein


Fall 2012

20

Protein Modeling
Challenge


2013 Event
Rules

www.stonybrook.edu/cesame



Pre
-
build model (40%)



On
-
site build (30%)



Written exam (30%)


Fall 2012

21

Estrogen Receptor


Pre
-
Built Model
2012


Protein Databank File 1A52 ESTROGEN RECEPTOR ALPHA LIGAND
-
BINDING DOMAIN COMPLEXED TO ESTRADIOL


Model should be based on residues 345
-
504 of chain A



Model must arrive at Stony Brook by 4:30 p.m. February 21. You can
mail or hand deliver it. If mailed be sure to have tracking information


Models are judge on:



structural accuracy


3
-
dimensional
topology


Clarity


Information


Include required
documents

Fall 2012

22

Written Exam
2013


Exam covers material in:



The Dynamic Structure of the Estrogen Receptor


Power Point Presentation from Bio364


Information taken from the following government sites:


http://www.cancer.gov/cancertopics/types/breast


http://www.uspreventiveservicestaskforce.org/index.html


http://www.cancer.gov/cancertopics/understandingcancer


Jmol


PDB file 1A52 and associated
abstract
http://www.pdb.org/pdb/explore/explore.do?structureId=1a52


Campbell,
Biology,

will be used a the material base for questions on
protein
structure and
function and cell communication.


Taken as a
group


Available at the exam will be:


PDB
file, abstract,


The structure summary page and sequence page for 1A52 from the Protein Data Bank


The molecule of the Month article


30
% team score


Fall 2012

23

Estrogen Receptor


On
-
site build


PDB file will be provided on the day of the
exam


Students will build a portion of the receptor. They will be given: a
toober, selected amino acid side chains, a computer,
jmol

and the
pdb

file.

Fall 2012

24

Protein Modeling Challenge With
National Science Content Standards


Science and Technology


Abilities of Technological Design


Understandings about Science and Technology


Life Science


The Cell


Physiology


Science as Inquiry


Abilities Necessary to do Scientific Inquiry


Physical Science


Structure and Properties of Matter


Chemical Reactions

Want More?

Bioinformatics sites for ESR alpha:


http://www.genecards.org/cgi
-
bin/carddisp.pl?gene=ESR1

Proteopedia

has an unimpressive
page
http://www.proteopedia.org/wiki/ind
ex.php/Estrogen_receptor

Cellular Landscapes at Cell Signaling

http://www.cellsignal.com/reference
/landscapes/nucleus.html

Fall 2012

25

Even More


See what scientist/artists can do with
information about Estrogen Receptors
at String 9.0
http://string
-
db.org/newstring_cgi/show_input_page.
pl?UserId=7yJna0cgDibk&sessionId=I6
X6eyfULPNe

admire the he image don’t try to learn the

Fall 2012

26