{"doi":"10.1021/acs.jpcb.5c01925","title":"Determining the Role of Electrostatics in the Making and Breaking of the Caprin1–ATP Nanocondensate","abstract":"We employ a multiscale computational approach to investigate the condensation process of the C-terminal low-complexity region of the Caprin1 protein as a function of increasing ATP concentration for three states: the initial mixed state, nanocondensate formation, and dissolution of the droplet as it reenters the mixed state. We show that upon condensation, ATP assembles via pi-pi interactions, resulting in the formation of a large cluster of stacked ATP molecules stabilized by sodium counterions. The surface of the ATP assembly interacts with the arginine-rich regions of the Caprin1 protein, particularly with its N-terminus, to promote the complete phase-separated droplet on a length scale of tens of nanometers. In order to understand droplet stability, we analyzed the near-surface electrostatic potential (NS-ESP) of Caprin1 and estimated the zeta potential of the Caprin1-ATP assemblies. We predict a positive NS-ESP at the Caprin1 surface for low ATP concentrations that defines the early mixed state, in excellent agreement with the NS-ESP obtained from NMR experiments using paramagnetic resonance enhancement. By contrast, the NS-ESP of Caprin1 at the surface of the nanocondensate at moderate levels of ATP is highly negative compared to that at the mixed state, and estimates of a large zeta potential outside the highly dense region of charge further explain the remarkable stability of this phase-separated droplet assembly. As ATP concentrations rise further, the strong electrostatic forces needed for nanocondensate stability are replaced by weaker Caprin1-ATP interactions that drive the re-entry into the mixed state that exhibits a much lower zeta potential.","journal":"The Journal of Physical Chemistry B","year":2025,"id":523251,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257872,"name":"Teresa Head‐Gordon","orcid":"0000-0003-0025-8987","position":1,"is_corresponding":false},{"id":1029839,"name":"Maria Tsanai","orcid":"0000-0001-5137-4174","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40314620","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}