This was intended as an article for the BPS 2024 blog but I was late in submitting. So here it is instead 😀
The Theory and Computation symposium continued on to their next speaker, Prof. Jessica Swanson from the University of Utah. She gave a bird’s eye view of her lab’s work on deciphering the kinetic rates of events. She highlighted that it is essential to know when kinetic selection between competing mechanisms/pathways is pivotal, a good example of which is kinetic proofreading in enzymes. Dr. Swanson noted that one only needs two things, a non-specific fast step followed by a specific slow step for this to work. She then described her lab’s work on the chloride channel and antiporter, the free energy landscape, and multistate kinetic model. The work involved using a master equation to determine the net flux, and they observed that the mechanisms were dependent on the pH. In her talk Dr. Swanson mentioned Prof. Benoit Roux’s 2021 book on “Computational modelling and simulation of biomolecular systems” as a comprehensive guide to studying kinetic models.
The next speaker was Prof. Glen Hocky from NYU who talked about how “proteins take their time under pressure”. Dr. Hockey mentioned their recent work shapeGMM to cluster simulation data based on a Gaussian distribution, and using metadynamics to get ensemble of clusters. Their objective was to see if conventional MD could be used to describe forces in actin-cytoskeleton. His lab used infrequent metadynamics by Tiwary and Parinello to get the correct kinetic rates from the biased simulation.
This was followed by Prof. Lynn Kamerlin from Georgia Tech-Uppsala University who talked about the importance of loop dynamics for enzymatic activity and conformational dynamics for new enzymes. Their lab has used bias-exchange metadynamics to do multiple simulations to create Markov State Models (MSM).
Apart from the T&C symposium there were two other talks I found interesting in the Membrane structure and function symposium. One was the Thomas E. Thompson Award talk that was given by the awardee Prof. Ed Lyman. He started off by talking about the evolutionarily interesting aspects of sterols. The biosynthetic pathway of cholesterol from squalene cannot happen without oxidation and thus puts the emergence of these molecules at a certain geological time. Cholesterol is a controversial molecule - it adds order by aligning the packing of lipids but it also makes the membrane more fluid. He highlighted other researchers in the field who have contributed to the understanding of lipids/cholesterol using experiments and simulations. He noted that cholesterol could protect cells under elastic stress since cholesterol can flip much faster than any other lipid. Lastly, he talked about recent developments in his lab on using machine learning to classify lipidomic data. Another membrane talk I attended was by Prof. Erdinc Sezgin from Karolinska Institute. Dr. Sezgin talked about their work on developing “smart” probes to measure membrane fluidity since many probes are not necessarily organelle specific. He differentiated between spectroscopic methods that give one value for a collection of data vs microscopic methods, which actually give us heterogeneous data. Flow cytometry falls in a sweet spot between the two. The goal was to study physiology of immune cells in blood. For this they developed single particle profiling (SPP) for lipid nanoparticles (LNP). Using this they can measure quantitative properties of the LNPs, such as how many copies of a certain protein are there and such.
After the talks, it was time for dinner and I got a few recommendations from friends. I have only tried two of these places but I am putting the list here in no particular order- Suraya (Mediterranean), Budakkan (Asian fusion), Penang (Malaysian), Hikari (Japanese), Tsaocca (bubble tea), dimsum garden (dimsum), Vedge (vegan), T-swirl crepe (dessert), A La Mousse (dessert), Frozen rolled ice-cream (dessert). I will be sure to keep this list in mind next time I visit Philly.
For corrections/suggestions please email me at jbodosa@umd.edu (Jessica Bodosa). Credit: I am grateful to Prakhar Gupta and Neha Nanajkar for proofreading the article.