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SUMMARY:A computational model for protein phase separation: hnRNPA1 as a c
 ase study - Maria Julia Maristany\, University of Cambridge
DTSTART:20220518T133000Z
DTEND:20220518T140000Z
UID:TALK169433@talks.cam.ac.uk
CONTACT:Lisa Masters
DESCRIPTION:First Year PhD Report:\nLiquid–liquid phase separation (LLPS
 ) is an important mechanism that contributes to intracellular organization
  via the formation of biomolecular condensates. From a theoretical and com
 putational perspective\, the development of accurate and transferable coar
 se-grained models that allow us to elucidate the molecular mechanisms driv
 ing condensate formation in the cytoplasm and nucleoplasm with attainable 
 computational cost is highly desirable.\nRecently\, Bremer and colleagues 
 provided an extensive set of experimental quantitative phase diagrams for 
 the low complexity domain (LCD) of the hnRNPA1 protein (A1LCD)\, an RNA bi
 nding protein that has been found to be involved in neurodegenerative dise
 ases\, in particular\, ALS. Our group has recently developed a multiscale 
 coarse-grained model\, termed ‘Mpipi‘ and based on atomistic potential
 -of-mean-force calculations\, which seeks to provide a balanced parametriz
 ation of interaction strengths between different types of amino acids\, ac
 counting for the dominant role of pi-based and other select interactions. 
 In this work\, we adopt Mpipi\, and compute phase diagrams for the full se
 t of A1LCD variants. We find excellent agreement between our simulated pha
 se diagrams and the experimental ones\, both qualitatively (i.e.\, the rel
 ative LLPS propensities of the proteins) and quantitatively (i.estimated c
 ritical temperatures for LLPS).\nDuring this talk\, I aim to give an overv
 iew of the theoretical framework of phase separation\, its importance in t
 he functionality and pathology of the cellular environment\, as well as pr
 esenting our new computational model and the insights we can learn from us
 ing the hnRNPA1 protein as a model example.
LOCATION:Wolfson Lecture Theatre\, Dept of Chemistry and Zoom
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