This was intended as an article for the BPS 2024 blog but I was late in submitting. So here it is instead 😀
On Saturday, I arrived by train just in time for a quick lunch at the Reading Terminal Market, and then for the Theory and Computation symposium. The historic market was crowded with BPS attendees and tourists, all of whom had decided to have lunch there. The market had a lot of local Philly specialties with a handful of vegetarian and vegan options.
The Theory and Computation symposium was chaired by Rommie Amaro of UCSD and she introduced the first speaker, Giulia Palermo of UC Riverside, who talked about using computational methods to study the dynamics of Crispr-Cas9. Dr. Palermo gave an overarching overview of her lab’s work on the allosteric activation of HNH and RuvC using enhanced sampling methods such as Gaussian accelerated MD (GaMD) and network analysis of the dynamics obtained from their simulations. Mutations were then added to the system in an attempt to enhance the specificity of the protein. These perturbations were assessed through changes in the interaction networks. Dr. Palermo also highlighted some of the QM work done by her lab and their recent paper on the CRISPR-Cas12a, where the alpha helical lid pushes the target DNA towards the catalytic site.
This was followed by Rosana Collepardo-Guevara from Cambridge who talked about her lab’s efforts in understanding the compaction of chromatin by liquid-liquid phase separation (LLPS). Dr. Collepardo-Guevara gave descriptive analogies of how chromatin compaction is akin to an extremely long strand of hair compacted into the size of a golf ball and that the final states could be thought of as paper folded into an origami boat or bird depending on the cues and environment. She highlighted that the high gene size and small resolution of chromatin condensates tends to fall in a blind spot of usual experiments. Her lab has worked on getting the phase diagram of chromatin phase separation dependent on the salt concentration. The phase diagram will help to study the emergent properties of chromatin. She defined ordered vs disordered organization of chromatin based on the uniform or non-uniform interactions of the nucleotides. Through their work, they have figured out the effect of ordered vs disordered interactions on chromatin phase separation. It makes one think, how the interactions, whether “orderly” or not, determine the final state of the compaction.
The third speaker was Kresten Lindorff-Larsen from the University of Copenhagen. The talk started off by Dr. Lindorff-Larsen showing the result of the poll he had put up on Twitter/X to choose which project to present that day, and IDP (intrinsically disordered protein) won the poll. The talk was on the coarse grain method to model IDPs developed by his lab called, CALVADOS. Dr. Lindorff-Larsen noted that structure prediction for IDPs is difficult mainly due to lack of a good database. Inspired by previous coarse grain models such as the hydrophobicity scale model, their method uses Bayesian learning to predict properties of IDPs. They found that their initial model, CALVADOS, was able to capture the propensity of IDPs to phase separate. The next iteration of their model, CALVADOS2 alpha had the coarse grain (CG) beads centred on the C-alpha atoms. In CALVADOS3 the CG beads were shifted to the centre of mass of the residues instead. This improved the performance for folded proteins. Their CALVADOS model gives good results for IDPs and can be run easily using a Google Colab and their ensemble data are available online. He also expressed appreciation for the valuable feedback received from the scientific community, acknowledging its improvement on his work, in particular the IDP Seminar series organised by Alex Holehouse.
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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.