Vibrational strong coupling in liquid water from cavity molecular dynamics.

We assess the cavity molecular dynamics method for the calculation of vibrational polariton spectra using liquid water as a specific example. We begin by disputing a recent suggestion that nuclear quantum effects may lead to a broadening of polariton bands, finding instead that they merely result in anharmonic red shifts in the polariton frequencies. We go on to show that our simulated cavity spectra can be reproduced to graphical accuracy with a harmonic model that uses just the cavity-free spectrum and the geometry of the cavity as input. We end by showing that this harmonic model can be combined with the experimental cavity-free spectrum to give results in good agreement with optical cavity measurements. Since the input to our harmonic model is equivalent to the input to the transfer matrix method of applied optics, we conclude that cavity molecular dynamics cannot provide any more insight into the effect of vibrational strong coupling on the absorption spectrum than this transfer matrix method, which is already widely used by experimentalists to corroborate their cavity results.

Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates.

Assemblies of multivalent RNA-binding protein fused in sarcoma (FUS) can exist in the functional liquid-like state as well as less dynamic and potentially toxic amyloid- and hydrogel-like states. How could then cells form liquid-like condensates while avoiding their transformation to amyloids? Here, we show how posttranslational phosphorylation can provide a "handle" that prevents liquid-solid transition of intracellular condensates containing FUS. Using residue-specific coarse-grained simulations, for 85 different mammalian FUS sequences, we show how the number of phosphorylation sites and their spatial arrangement affect intracluster dynamics preventing conversion to amyloids. All atom simulations further confirm that phosphorylation can effectively reduce the ß-sheet propensity in amyloid-prone fragments of FUS. A detailed evolutionary analysis shows that mammalian FUS PLDs are enriched in amyloid-prone stretches compared to control neutrally evolved sequences, suggesting that mammalian FUS proteins evolved to self-assemble. However, in stark contrast to proteins that do not phase-separate for their function, mammalian sequences have phosphosites in close proximity to these amyloid-prone regions. These results suggest that evolution uses amyloid-prone sequences in prion-like domains to enhance phase separation of condensate proteins while enriching phosphorylation sites in close proximity to safeguard against liquid-solid transitions.