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bioRxiv · 10.1101/2025.11.09.687447

CASPULE: A computational tool to study sticker spacer polymer condensates

Chattaraj, A.·Kanovich, D. S.·Ranganathan, S.·Shakhnovich, E. I.
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Abstract

Phase separated condensates are recognized as a ubiquitous mechanism of spatial organization in cell biology. Biophysical modeling of condensates provides critical insights into the dynamics and functions of these subcellular structures that are difficult to extract via experiments. Here we present an efficient computational pipeline, CASPULE (Condensate Analysis of Sticker Spacer Polymers Using the LAMMPS Engine), to simulate and analyze the biological condensates made of sticker-spacer polymers. CASPULE implements a unique force field that combines traditional Langevin dynamics with a "detailed-balance proof" protocol for single-valent bond formation between stickers. This framework allows us to study the nontrivial biophysics that emerge from singlevalent sticker interactions, coupled with the effect of separating the energetic contributions of stickers and spacers. We provide detailed documentation on how to setup the simulation environment, perform simulations and analyze the results. Through case studies, we highlight the utility and efficacy of our pipeline. Importantly, we provide statistical parameters to characterize the cluster size distribution often observed in biological systems. We envision this tool to be broadly useful in decoding the interplay of kinetics and thermodynamics underlying the formation and function of biological condensates. Code and documentation: https://caspule.github.io/caspule/ Author SummaryLiving cells contain droplet-like compartments called biomolecular condensates that organize important molecules and reactions without a surrounding membrane. Understanding how these condensates form and behave helps us learn more about healthy cellular function and diseases. Condensate forming biopolymers (proteins and nucleic acids) often contain a sticker spacer architecture that gives rise to interesting emergent properties when they assemble into a condensate. Here we report an easy-to-use computational pipeline, called CASPULE, that allows us to simulate and analyze the condensation of polymer chains. Unlike previous tools, CASPULE models both the physical motion of these molecules and specific bonding interactions between sticker segments. This user-friendly tool will enable researchers to explore the governing principles underlying the formation and function of biomolecular condensates.

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Chattaraj, A., Kanovich, D. S., Ranganathan, S., Shakhnovich, E. I.. 2025-11-10. CASPULE: A computational tool to study sticker spacer polymer condensates. https://doi.org/10.1101/2025.11.09.687447

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