Possible Outline for the Capstone Presentation

• When relevant, I recommend using the online software BioRender. Student accounts are free and it is very easy to use.

Basic Outline

1. Biological Target
   1. Background
   2. Localization
   3. Function
   4. Structure
   5. Mechanism
2. Drug
   1. Backgound
   2. Properties
   3. Clinical Relevance
   4. MS Spectrum
   5. NMR Spectrum
3. Drug-Biological Target
   1. Drug Binding Sites
   2. Drug's Pharmacophore
4. New Lead Drug
5. Drug Development Process with your New Lead Drug

Detailed Outline

1. Biological Target Background
   1. When was it discovered?
   2. Why is it important?
   3. What role does general role does it play in physiology?
   4. What diseases does it affect?
2. Where is your biological target expressed?
   1. What organs is it expressed in?
   2. What type of cells is it expressed in?
   3. Where in the cell is it expressed?
3. How does your biological function?
4. Describe the structure of the biological target?
   1. What is the two dimensional topology?
   2. X-ray crystal structure, Cryo-em, or homology model.
5. Describe a detailed mechanism of the biological target?
6. Drug Background
   1. Describe how your drug is synthesized or extracted from a plant source?
   2. What is the history of your selected drug?
7. Describe the properties of your drug
   1. If you did Assignment #3, describe the properties that you determined of your drug.
      1. If your drug is a small molecule, chemoinformatics.
      2. If your drug is a large protein biologic like an antibody, bioinformatics.
   2. If you did not do Assignment #3, describe the published properties of your drug.
8. Clinical Relevance
   1. Pharmacodynamics (PD)
   2. Pharmacokinetics (PK)
   3. Administration Route
9. Mass spectra of your drug with fragmentation assignments (experimental and simulated).
   1. https://webbook.nist.gov/chemistry/name-ser/
   2. https://spectrabase.com/
   3. https://fluorine.ch.man.ac.uk/research/mstool.php
   4. https://www.protpi.ch/Calculator/MassSpecSimulator
   5. https://chemdata.nist.gov/dokuwiki/doku.php?id=peptidew:mspepsearch
   6. https://sdbs.db.aist.go.jp/sdbs/cgi-bin/cre_index.cgi
   7. Search online for articles for experimental information.
10. NMR spectrum of your drug with assignments (experimental and simulated).
    1. https://webbook.nist.gov/chemistry/name-ser/
    2. https://spectrabase.com/
    3. https://www.nmrdb.org/
    4. https://sdbs.db.aist.go.jp/sdbs/cgi-bin/cre_index.cgi
    5. Search online for articles for experimental information.
    6. If you picked a drug that is too difficult to simulate by NMR such as large biologic, describe how you would determine it by NMR.
11. Describe known drug/substrate/ligand binding sites
    1. If you did Assignment #6, describe drug binding site to your target protein after docking.
       1. If your is a large protein biologic, then you dock it with ClusPro. A description of the interactions of a biologic with its target will be a lot broader than for a small molecule drug.
       2. For all other drugs, then dock it with SwissDock.
       3. For a SwissDock or ClusPro docking simulation, please be sure to show all your parameters and explain your rational.
       4. The compare your docking with known drug/ligand/substrate binding sites.
    2. If you did not do Assignment #6, describe the known binding sites of your drug to the biological target.
12. Develop a pharmacophore of your drug based on drugs in the same class and explain your rational.
    1. If your drug is a biologic like an antibody, you might use the interacting region as a pharmacophore. In the case of an antibody, you might pick a different peptide fragment of the target protein to serve as an antigen. Explain the rational of picking that peptide fragment to target. Basically, you want to develop a biologic that will interact with the same biological target.
    2. If your drug is a small molecule, then design a pharmacophore based on similar drugs within the drug class. What do drugs in the same drug class have in common? Pharmacophores can be quite simple.
13. Based on the pharmacophore that you made, describe how you would find a new drug lead.
    1. If your drug is a small molecule, find new leads with ZincPharmer. Only show the top 10 hits on ZincPharmer.
    2. If your drug is a biologic like an antibody, describe how you make new biologics against your biologic target.
14. Describe the drug development process with your new drug lead.