(515f) Assemblies of Multi-Component Intrinsically Disordered Proteins and Their Spatial Organization

The assembly of intrinsically disordered proteins (IDPs) has recently gained lots of attention due to their pivotal role in forming many protein complexes or membrane-less organelles. Being intrinsically disordered, they exhibit flexible conformation which mediates their interactions with many biomolecules. However, the understanding of the complicate interactions in the assembly of IDPs is still limited. Here, we employed coarse-grained modeling to unveil the mechanism of the assembly of IDPs. Previous computational studies mostly reported single-component IDP systems. The investigation of multi-component IDP systems still lacks. To address this knowledge gap, we designed different types of IDPs with a range of net charges, from neutral to highly charged IDPs. The binary and ternary mixtures of IDPs with different net charges were built. We found the total net charge of the system determines if aggregation or phase separation occurs. Furthermore, the net charge also significantly affects the size distributions of the aggregates and/or the morphology of the phase-separated condensates. The unsupervised machine learning algorithm is performed to characterize the aggregates and condensates of IDP mixtures. This work would provide insight into the precise control of the assembly of IDP mixtures in the cellular processes for potential therapeutic goals.