Valency-Limited Molecular Dynamics Simulations of Stickers-and-Spacers Polymers Reveal a Trade-Off between Condensation and Organization

Biomolecular condensates formed by intrinsically disordered proteins (IDPs) are often described using stickers-and-spacers models, in which specific sticker motifs form reversible cross-links and spacer regions modulate phase behavior. Recent theory predicts that heterogeneous nonspecific spacer interactions can promote condensation but may also disrupt sticker-mediated organization. Here, we develop an off-lattice coarse-grained stickers-and-spacers polymer model for continuous molecular dynamics simulations and implement it in the GPU-accelerated OpenABC package. The model uses a directional sticker–sticker interaction to encode limited valency through interaction geometry, producing effectively one-to-one sticker binding without explicit bond assignment. Simulations of one-component systems show that sticker affinity and multivalency promote porous, network-like condensates, while nonspecific spacer interactions can also drive phase separation but produce more compact, spacer-dominated dense phases. When both interaction types are present, strong spacer heterogeneity reduces sticker conversion, suppresses sticker mobility, and disrupts the sticker-mediated network. In two-component systems, specific sticker interactions buffer client recruitment into host condensates, while nonspecific spacer interactions produce reservoir-dependent uptake. These results support a trade-off in which spacer heterogeneity promotes condensation at the cost of condensate organization and compositional robustness, providing a physical rationale for the suppression of promiscuous spacer interactions in low-complexity IDP regions.