Biological Target Project

To earn a C or higher, you must complete a small research project and give a satisfactory presentation about the scientific and business prospects of developing a ligand for a biological target of your choice. To earn a B or higher, you must also complete a satisfactory report. As mentioned in the syllabus, an unsatisfactory presentation or report may be revised with 2 tokens.

Research

The research project includes the following steps:

  • Search for and select a personal target to do further research on. The target or a close homolog must have a public crystal structure in the Protein Data Bank (https://www.rcsb.org). After making sure that nobody has selected the same target, enter your name and target in the Google spreadsheet.
  • Download and at least partially read at least five references related to your target.
  • Perform structural analysis and visualization and at least two of the following:
    • homology modeling,
    • structural alignment,
    • or electrostatics calculations.

Some targets that you may find interesting are:

  • µ-opioid receptor (which Bing is studying)
  • BaxΔ2 (which Ricky is studying)
  • Cytochrome P450s from Western Corn Rootworm (which Nick is studying)
  • Tyrosyl-DNA phosphodiesterase 1 (TDP1), a possible cancer drug target

Presentation

In the presentation, you should address the following questions:

  • Why is the target interesting?
  • What are the potential societal benefits of designing ligands that bind to the target? For example, what is the evidence, e.g. mechanistic rationale or mutations observed in the clinic, that such a ligand is likely to affect the progression of a disease?
  • How suitable is the target for structure-based drug design? What structural information is available and what is the quality of this information? What is the structural or anecdotal evidence the the target is druggable? What other proteins may also be affected by a ligand that binds to the target?
  • What are the business prospects of a molecule that interacts with the target? For example, how many people are affected by the related diseases and where do they live? Are there already other safe and effective treatments for the same diseases?

The presentation should be 12 minutes long, followed by 3 minutes for questions.

As a visual aid to your presentation, you should prepare a series of slides that present evidence for your answers based on your own work as well as data and figures from other sources. For example, you could perform a structural alignment between the binding site of the bacterial and human homologue of your target to highlight structural differences. This may provide evidence that a ligand that binds to the bacterial site is unlikely to also bind to the human site, or vice versa. (You may also present some calculations that do not directly address the questions.) Data and figures from other sources should be properly cited. Citations should be numbered/named on individual slides and an ACS-style bibliography included at the end of the slide slow. The slide show should be in Apple Keynote (.key), Microsoft Powerpoint (.ppt/,pptx), Google Slides (.gslides), or Portable Document Format (.pdf) format. Before the first student presents, your slides should be saved in a folder within your class folder as BiologicalTarget/BiologicalTargetPresentation.XXX, where XXX is the file extension. To expedite transitions between presentations, students will all present using the instructor’s laptop.

A satisfactory presentation will

  • address all of the questions with sufficient evidence for the answers,
  • include the required calculations,
  • cite references properly, and
  • be clear and concise, within the specified time slot

Report

The report is a written version of the presentation. You should address the same questions and present evidence in the text and in figures and tables. The report should be at least three pages long and saved as a document in Apple Pages (.pages), Microsoft Word (.doc/.docx), Google Document (.gdoc), or Portable Document Format (.pdf) format.

Before 11:25am on the due date, your report should be saved in a folder within your class folder as BiologicalTarget/BiologicalTargetReport.XXX, where XXX is the file extension.

A satisfactory report will meet the same criterion as the presentation except for the last. Instead, the report should be clearly written with proper English spelling and grammar.

Pharmaceutical Ethics Report

To earn a C or higher, you must write a satisfactory summary of the discussion related to pharmaceutical ethics. As described the syllabus, the length of the summary will depend on the grade that you are trying to earn. To be satisfactory, the summary must cover key points from the discussion and be clearly written with proper English spelling and grammar.

The report should be saved as a document in Apple Pages (.pages), Microsoft Word (.doc/.docx), Google Document (.gdoc), or Portable Document Format (.pdf) format. Before 11:25am on the due date, your report should be saved in your class folder as PharmaceuticalEthicsReport.XXX, where XXX is the file extension.

Final Project

To pass this class, you must work in teams of 3 or 4 members to complete a research project that uses some of the molecular modeling methods that we have learned about in this class to study a biological target selected by one of the members. Your team must also give a final presentation, present your findings at Innovation Day, and write a final report. Finally, to earn a C or higher, you must write a report that describes your individual contributions to the project.

Research

Your team should propose, design, and perform a rational series of calculations involving the selected biological target. To pass the class, your team must perform at least one molecular docking and one molecular dynamics simulation and appropriate analyses. To earn a B or higher, your project should have a clear contribution to science - to explain an experimental observation, to make predictions about a biological macromolecule, or both.

You will almost certainly need to perform additional calculations to achieve this goal. These may be based on the same methods you used for the Biological Target Project, e.g. structural alignment, homology models, or electrostatics. As another example, you may want to perform a virtual screen of a library of compounds against the target. As yet another example, you may perform a binding free energy calculation to obtain a more accurate prediction of the binding pose or affinity. In any case, I strongly encourage you to talk to me about the feasibility of your planned calculations.

Presentation

Your presentation should have the following sections that address specific questions:

  • Introduction. What was the motivation for your calculations? What was known about your target and what were the open questions?
  • Results. What data were produced by your calculations? Data could include structures such as binding poses, average structural quantities, energies and free energies. They could be visualized in various types of figures and tables. If helpful, you may present data from the Biological Target Report. What do the calculations explain or predict about the biological target?
  • Discussion. How do your results fit in with the scientific literature? Are they consistent or contradictory? Were the results expected or unexpected?
  • Future Directions. What additional calculations or experiments could potentially be done? Would would you expect to learn from them?
  • Conclusion. Based on all your results and in the context of the scientific literature, what did you learn?
  • Methods. What calculations did you perform and how did you do them? You may not actually present this section, but you should have slides in case there are questions about it.

In general, the sections should be in this order. However, if the Methods are not standard, you may want to include them between the Introduction and Results.

The presentation should be 35 minutes long, including questions.

As with the Biological Target Presentation, you should prepare a series of slides to accompany your presentation. Data and figures that you did not generate should be properly cited. Citations should be numbered/named on individual slides and an ACS-style bibliography included at the end of the slide slow. The slide show should be in Apple Keynote (.key), Microsoft Powerpoint (.ppt/,pptx), Google Slides (.gslides), or Portable Document Format (.pdf) format. Before the first team presents, your slides should be saved in a folder within your class folder as FinalProject/FinalPresentation.XXX, where XXX is the file extension. To expedite transitions between presentations, students will all present using the instructor’s laptop.

A presentation that enables the team to pass the class will

  • address all of the questions with sufficient evidence for the answers,
  • include the required calculations,
  • cite references properly, and
  • be clear and concise, within the specified time slot

A presentation that enables the team to earn an A or B will describe a clear contribution to science. To enable the team to earn an A, the presentation must have the polish of a conference presentation. Conference presentations are well-organized and smoothly delivered. Moreover, presenters are knowledgable about the background and are able to answer most questions intelligently.

Innovation Day

For specifications of Innovation Day poster presentations, see the lecture slides from 11/16.

Report

The final report should capture the team’s project work in the format of a scientific journal. Fortunately, the sections of the presentation reflect this format; as with the Biological Target presentation and report, the report is a written version of the presentation. You should address the same questions and present evidence in the text and in figures and tables. Unless approved for another journal, the document should be prepared for submission to the Journal of Chemical Information and Modelling according to the journal’s author guidelines. It should be saved as a document suitable for submission to the journal. If there is a clear scientific contribution, the team may be encouraged to actually submit the paper for publication.

Before 11:25am on the due date, your report should be saved in a folder within your class folder as FinalProject/FinalReport.XXX, where XXX is the file extension.

A satisfactory report will meet the same criterion as the presentation except for the last. Instead, the report should be clearly written with proper English spelling and grammar.

A report that enables the team to earn an A or B will describe a clear contribution to science. To enable the team to earn an A, the presentation must have the polish of a journal article. Journal articles are well-organized and written logically with citations for every claim that is not common knowledge. Figures and table should clearly convey information that is discussed in the text. All conclusions should be clearly supported by the data. Submitted manuscripts that do not meet these requirements are likely to be rejected or require major revision. If I deem the article acceptable as is or with only minor revisions, then the team will have the opportunity to earn an A.

Individual contribution summary and project portfolio

To earn a C or higher, you must write a report (1 page or longer) that includes two sections:

  • an individual contribution summary and
  • a project portfolio.

In the individual contribution summary, you should summarize how you contributed to the final project. For some examples of ways that you may have contributed to the project, see the PLOS guidelines for author contributions. The PLOS guidelines were developed for a journal article. Additional ways that you can contribute are preparing the presentation slides or poster or presenting these materials before the class or during Innovation Day.

For the project portfolio, you should describe the skills that you have developed over the course of the project. These skills could be technical skills related to the calculations. They could also be “soft” skills related to teamwork, project management, interpersonal relationships, communication, presentation, and writing. Preparing this project portfolio could help you answer job interview questions in the future.

This report will be a major factor in your “Individual contribution to final project” grade.