The document describes using systems biology modeling tools to model the metabolic network of MRSA acetate kinase. It outlines conducting protein homology modeling using PMP to generate structural models of acetate kinase, evaluating models using ERRAT, chemical modeling of protein kinase inhibitors using OCHEM and PubChem, and metabolic network modeling using BioModels and Virtual Cell. The aim is to understand how protein, chemical, and metabolic network modeling can provide more information for research into new antibiotic targets. Key steps include selecting templates for homology modeling, evaluating models with ERRAT, extracting chemical data from OCHEM and PubChem, importing an acetate kinase model from BioModels into Virtual Cell, validating the model, and running simulations in Virtual Cell.

1. Systems Biology and Protein
Homology Modeling
Theme: MRSA Acetate Kinase and Metabolic
Network Modeling
Lab #2
Etienne Z. Gnimpieba
BRIN WS 2013
Mount Marty College – June 24th 2013
Etienne.gnimpieba@usd.edu

2. Context
0. Specification & Aims
Lab #2
Statement of problem / Case study:
MRSA Acetate Kinase ( SAV 1711 from MRSA Mu50 strain) was found in our preliminary study on Silico. It is essential to bacteria growth and absent in humans. Currently, there
is no FDA approved antibiotics targeting bacterial central metabolism, these bacterial sites have not yet been exposed to antibacterial agents and therefore will be less likely to
develop a drug resistance.
Modeling
Keywords:
Bio: MRSA, Acetate Kinase
Informatics: programing, bioinformatics tools, getting
and exporting data. Validating models.
16 Korean Bioinformation Center, 2010
Reduced expression of frataxin is the
cause of Friedrich's ataxia (FRDA), a
lethal neurodegenerative disease, how
about liver cancer?
Aim: The purpose of this lab is to understand
how Protein, Chemical, and Metabolic
Network Modeling can be used for research
topics. This process will allow researchers
more information to have more information
available.
Acquired skills
Online and server tools:
- Protein Homology Modeling
- Model Evaluation on ERRAT
- Chemical Modeling through OCHEM server
- Metabolic Network Modeling using BioModels and Virtual
Cell.
Biological Hypothesis
2
Resolution Process
T2. Chemical Modeling
Objective: Use of OCHEM and PubChem to extract information about the desired chemical models.
T3. Metabolic Network Modeling
Objective: Use of BioModels and Virtual Cell to extract data about Metabolic
Networking.
T2.1. Using OCHEM and PubChem
T3.1. Finding a model using BioModels
T3.2. Validating the Model
T3.3. Virtual Cell
T1. Protein Homology Modeling (PMP)
Objective: Use of PMP website to evaluate different protein models via the ERRAT
website.
T1.1 Template Selection
T1.2. Model Evaluation on ERRAT

3. Protein Modeling Systems Biology and Protein Modeling
T1. Protein Modeling
Objective: Use of PMP website to evaluate different protein models via the ERRAT website.
T1.1. Template Selection
On the Protein Modeling Portal website: http://www.proteinmodelportal.org
1) Click on “interactive modeling” and put in your Name and E-Mail address (results will be sent to your e-mail)
2) Copy and paste the amino acid sequence from the word document “Amino Acid Sequence”
3) Check all six boxes below (the different Databases used) Be sure to select the first option under ModWeb and
the check the box under M4T.
4) Submit Query
5) Once execution has gone through, select the different Database results. Because this query takes a long time we
have the finished results available.
6) Open jmol, then go to “File”, “Open” and open the file in your student folder called “Swiss Model Result” (a pdb
file)
Etienne Z. Gnimpieba
BRIN WS 2013
Mount Marty College – June 24th 2013
T1.2. Model Evaluation on ERRAT
Will have many models, in order to select best fitting model we use model evaluation tools such as ERRAT.
On ERRAT website: http://nihserver.mbi.ucla.edu/ERRATv2/
1) Click “browse” (or “choose file”) and select the PDB file “Swiss Model Result.pdb” in your folder and click
“send file”
2) The results will open and you can look at the information provided such as the quality of the model chosen.
3) Open the PDF version by clicking on “PDF file here” and save.
4) You can do this with all of the models you receive in your e-mail and compare the quality of each in order to
chose the best model

4. Chemical Modeling
T2. Chemical Modeling
Objective: Use of OCHEM and PuubChem to extract information about the desired chemical
models.
T2.1. Using OCHEM and PubChem
On the OCHEM website: http://www.ochem.eu/home/show.do
o Click on “Run predictions” and “login as guest”. Accept the “Terms and Agreements” form
o Then select all the boxes under the “What would you like to predict?”
o Then open a new tab and go to the PubChem website: http://pubchem.ncbi.nlm.nih.gov/
o Search under the “Compound” tab for “protein kinase” and select the “protein kinase inhibitor M (6-24)”
o Scroll down and copy the sequence from “canonical SMILES” and paste to the “Provide Name/CAS-
RN/SMILES” on OCHEM website
o Select the “Provide Name/CAS-RN/SMILES” and click “Run predictions”
o Once results show up you can read and deduce the information provided.
Etienne Z. Gnimpieba
BRIN WS 2013
Mount Marty College – June 24th 2013
Systems Biology and Protein Modeling

5. Metabolic Network Modeling
T3. Metabolic Network Modeling
Objective: Use of BioModels and Virtual Cell to extract data about Metabolic Networking.
T3.1. Finding a model using BioModels
On the BioModels website: http://www.ebi.ac.uk/biomodels-main/
o Search “acetate kinase” select the 3rd, “Cell Cycle 6var”
o Place your mouse over “Download SBML” in the top left of the screen, and select “SMBL L2 V4 (curated)” and
save the file. This file will already be in your Student Folder as “AcetateKinaseModel.xml”
Etienne Z. Gnimpieba
BRIN WS 2013
Mount Marty College – June 24th 2013
T3.2. Validating the Model
On the SMBL Validator website: http://sbml.org/validator/
o Click “Browse” and open the “AcetateKinaseModel.xml”
o Click “Validate Now” and check its validity
Systems Biology and Protein Modeling
T3.3. Virtual Cell
o Go to your Student Folder in “Tools” and run “vcell”. Exit the boxes that pop up
o Click on “Reactions” tab and double click “add new here” in the center
o On the left side of the arrow put an “S” (for substrate) and on the right side put a “P” (for product) [S -> P]
o Push enter to create your reaction
o Make sure you are still on the new reaction and pull down “Kinetic Type” at the bottom and select “Henri-
Michaelis-Menten (Irreversible)..”
o Edit the “Expression” for “Km” to be “0.01” as well as the “Vmax” to be “10.0” by double clicking under “Expression”
o Click on the “Applications” on the left, pull down “Add New” in the middle and select “Deterministic”
o Click on “Application: Application0”
o Click “New Simulation” [ ] then click “Edit” [ ]
o A window will pop up, adjust value under “Default” by clicking the box under “Scan” for; “P_init_uM” to min “0.1”
and max “100”; “S_init_uM” to min “0.1” max “100”
o Click “ok”
o Push the play button [ ] in the upper right corner to simulate the model
o The results will pop up in a new window. You can choose which results you see by selecting them on the left