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Biomolecular coacervates, or condensates, are dynamic cellular compartments made of proteins and nucleic acids, and form via phase separation. Coacervates play critical roles in cell function, including transcription and translation, genome regulation, and more. As such, abnormalities and aggregation of coacervates have been associated with various diseases, including ALS, cancers, and neurodegenerative diseases. We aim to model coacervation computationally to study the biophysics of these systems at a submolecular resolution. To do so, we must correctly account for relative interaction strength of constituent molecules to accurately recapitulate phase behavior. The multiscale pi-pi model (Mpipi) developed by Joseph and colleagues (2022) is currently one of the few models which predicts phase behavior of disordered proteins with quantitative accuracy while coarse-graining at one bead per residue. However, the role of electrostatics versus other short-ranged non-bonded interactions is not well understood, as it has not been extensively studied. This study aims to examine and recalibrate Mpipi parameters against experimental results of Choi and colleagues (2022) to better capture effects of electrostatics on condensate formation. Choi and colleagues showed that decapeptide systems of arginine, lysine, and aspartic acid formed homogenous (R10/D10 and K10/D10) or multiphasic (R10/K10/D10) droplets in vitro. We use the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS), a molecular dynamics simulator, along with Mpipi parameters to model these systems. Under initial parameters, no coacervation occured in any of the systems. Changing charges to ±1.0 rather than ±0.75 allowed coacervation to occur, though no multiphasic droplets formed in the R10/K10/D10 system. Preliminary testing for various Debye lengths (to simulate ion-screening effects) did not seem to significantly affect coacervation or phase behavior. Contrary to experimental findings, mapped phase diagrams revealed that the K10/D10 coacervate was found to be more stable than the R10/D10 coacervate (indicated by a higher critical temperature). Future studies may focus on adjusting parameters such that multiphasic droplets form and relative stability agrees with experiments. Thanks to the Princeton Center for Complex Materials Research Experience for Undergraduates (PCCM REU). Funded by the National Science Foundation (NSF) award 2011750.
Nguyen et al. (Fri,) studied this question.