What is Structural Biology? It is a study of protein structures across the hierarchy, using experimental and computational techniques to recover the structures, hence using biophysics to extract information about their structural-functional relationship.
In these two weeks, we have been exposed to a number of softwares used in structural biology, with Pymol being the obvious one for visualising protein and making short animations out of this (It crashed numerous times on my DTC computer and apparently managed to remove Okular upon its crash on one of my colleague’s computer…). Then we set up some Molecular Dynamics simulations using different packages and a few settings of force fields.
At the end of the first week, we spent two days at the Structural Genomics Consortium near the Churchill Hospital. We learnt about the pipeline of X-ray crystallography of proteins: from expression screening, construct design, purification, mass spectrometry, high throughput screening for small molecular binders, crystalisation, cryocooling through to the X-ray machinery. Each group of four students participated in two practicals, and produced a poster to discuss our results from these practicals. For my group, we studied how one can use software to extract the electron density map from X-ray crystallography data, construct the molecular structures based on homologs, then carried out iterative molecular replacement to find the structure of best fit. We also examined potential discrepancies on these reconstructed structures especially around small ligands and B-factor values. Our second practical involved an exposure to a wide range of machines for high throughput compound screening, deducing their affinities and binding energies through techniques such as the Isothermal Calorimetry. Obviously, doing these by hand is not the ideal practice – therefore we were also stunned with a robotic arm which can do it in 10 minutes, that left us totally amused… At the poster session, we explained to each other what we have done and how useful the techniques are for structural biology research- and what to be aware of while we interpret the data or use it to calibrate for other purposes.
The second assignment was a short film production to portray different aspects of molecular dynamics. Our group picked the topics on Free Energy Calculations. What is Free Energy Calculations? Let’s watch this: