Asymmetric_Immiscibility_Simulations

This is a repository of Python scripts associated with the manuscript "Asymmetric oligomerization state and sequence patterning can tune multiphase condensate miscibility" published on Bioxriv on March 12, 2023, and all subsequent versions of this manuscript. It contains simulation scripts for MD software HOOMD-Blue 2.9.7 with the plugin azplugins to perform direct coexistence NPAT simulations for estimating the relative miscibility of model disordered proteins with oligomerization effects.

Example Usage

1. In folder InitialConfig, the script GenInitConfig.py creates an initial configuration by initializing a system of 147 KE1x3 star polymers and 441 KE7 polymers in a cubic box, taking as input a pre-equilibrated configuration of a single KE1x3 polymer in start_ke1_3arm.gsd. An initial configuration file named start_ke1.gsd is created.
2. This intial configuration file is then utilized by the script SlabResize.py in folder NVT to compress the cubic box to a size 20nm³ at constant temperature T=250K, following which the z-dimension of the simulation box is extended to 120nm by unwrapping the coordinates, to produce a configuration file box2slab_extend_250.gsd.
3. A direct coexistence NVT run is then performed by the script SlabEquilibrate.py at T=250K to equilibrate the system and produce coexisting dense and dilute phases. This produces a trajectory file named restart_tmp1_250.gsd.
4. The equilibrated simulation trajectory from the NVT run is then utilized to perform a direct coexistence NPAT simulation using script SlabNPATProduction.py. The final production simulation trajectory of the NPAT can then be analyzed to investigate the miscibility of model disordered protein sequences and its dependence on oligomerization state and sequence identity.

Acknowledgments

Code for setting up the HPS interaction model and NVT simulations was adapted from slab_builder. Regy, R. M.; Zheng, W.; Mittal, J. Theory of biological phase separation, Liquid-Liquid Phase Coexistence and Membraneless Organelles. in Liquid-Liquid Phase Coexistence and Membraneless Organelles (ed. Keating, C. D.) (2020).