One of the most useful ways I prepared for my viva was by asking people who worked on similar PhD projects about their vivas and what they were asked. Below is a detailed but non-exhaustive list of questions and concepts I vaguely remember talking about during my viva. I hope it is useful as a guide for any current medicinal chemistry PhD students out there!
[Disclaimer: these questions are very specific and have quite a lot of jargon in them – apologies, but I put them in this post on purpose. PhDs involve you becoming an expert in a niche subject so I’d only expect another medicinal chemist googling for viva tips like I was a couple of months ago to find some of the actual content useful, however I hope more generally it shows what the process of the viva involves.]
Introduction
- Target-based vs. probe-based strategies in drug discovery – essentially talking through my first figure
- Differences between a chemical probe and a drug
- Different criteria in the literature for what makes a good chemical probe
- Should you develop a probe with in vivo studies in mind?
- Starting points in a drug discovery project (literature screen, in silico screen, fragment screen, HTS library screen, patent hopping), advantages and disadvantages of all these techniques
- Target protein’s location in cells and if ubiquitous expression is of concern for it being a drug target of interest
- Importance of selectivity in early phase/late stage drug discovery
- Techniques for identifying disease targets (mice knockouts, cell knockouts, induced knockouts)
Results chapters
- Whether I did the computational chemistry (I did!)
- Usefulness of the molecular docking I did
- Why I used the software I did
- Role of DMAP in a particular reaction
- Drawing the chemical structure of DMAP
- How I would correct my schematic of a palladium-catalysed cycle (cringe!)
- Examples of more advanced Pd-catalysts
- The two mechanism theories currently proposed for Suzuki-Miyaura coupling reactions
- What the Z-value stands for in my assay data and how it was calculated
- How a particular assay worked (DiscoverX KINOMEscan)
- Discrepancies in TR-FRET data
- Identifying and describing an SN2-type reaction
- Geometry of transition state in SN2 reactions
- Drawing the reaction energy profile of an SN2 reaction
- Solubility of my compounds
- Ligand efficiency of my compounds
General questions
- If I found the international collaboration involving my project worked well
- What I’d do next
Experimental methods chapter
- Why I saw two peaks for a particular bond in an IR spectra (stretch/bend)
- Stereochemistry assignment of one of the chiral centres of one of my compounds – asked to name Carr Ingold Prelog rules used to do this
- Diastereotopic protons
- Double checking NMR assignments (some doublets were actually just very close singlets)
Other things I revised that didn’t come up
- pKa values of important protons in all reactions
- LogP values of my compounds
- All reaction mechanisms
- Being able to draw all the abbreviated chemical structures in my thesis
- Structures of amino acids
- How all assays worked
- Roles of reagents
- Alternative reagents/reactions – but not every example under the sun!
- Enzyme kinetics, deriving Mendel-Michaelis equation etc.
- The difference between IC50/Ki etc.
- When examples of FDA approved drugs and other compounds I’d given were approved, what they treated and how they were made
- Polar surface area of all compounds
- Overview of how chemical analysis techniques worked (e.g. NMR, mass spectrometry)
- Reasons for going in particular directions with the project
- Work by my examiners
This all might be way too specific for the average reader of this blog but it’s the sort of stuff I wanted to know before my viva about how someone else’s had gone.
Oh wow, this list is great! Thanks for sharing!
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