Small molecule properties define partitioning into biomolecular condensates

Biomolecular condensates regulate cellular function by compartmentalizing molecules without a surrounding membrane. Condensate function arises from specific exclusion or enrichment of molecules. Thus, understanding condensate composition is critical to characterizing condensate function. While principles defining macromolecular composition have been described, understanding of small molecule composition remains limited. Here we quantified partitioning of ~1700 biologically relevant small molecules into condensates composed of different macromolecules. Partitioning varied nearly a million-fold across compounds but was correlated among condensates, indicating disparate condensates are physically similar. For one system, enriched compounds did not generally bind macromolecules with high affinity under conditions where condensates do not form, suggesting partitioning is not governed by site-specific interactions. Correspondingly, a machine learning model accurately predicts partitioning usi..., , , # Small molecule properties define partitioning into biomolecular condensates

[https://doi.org/10.5061/dryad.fxpnvx10r](https://doi.org/10.5061/dryad.fxpnvx10r)

The data set provided here consists of raw data files used for determining the partitioning coefficient (PC) data. This calculation is based on the area under the curve (AUC) analysis of metabolites or FDA-approved small molecule drugs. These small molecules are detected and measured their AUC using either targeted or untargeted metabolomics approaches via mass spectrometry.

The second set of data comprises measurements from Isothermal Calorimetry. These measurements focus on the binding of small molecules to proteins.

The third category of data sets includes microscopy data. Specifically, these data set includes the measurements for the partitioning of fluorescent drugs into biomolecular condensates. The acquisition of these data sets is facilitated through confocal fluorescence microscopy.

## Description of the data and f...