A unified analytical theory of heteropolymers for sequence-specific phase behaviors of polyelectrolytes and polyampholytes
Bibliographic record
Abstract
The physical chemistry of liquid-liquid phase separation (LLPS) of polymer solutions bears directly on the assembly of biologically functional dropletlike bodies from proteins and nucleic acids. These biomolecular condensates include certain extracellular materials and intracellular compartments that are characterized as "membraneless organelles." Analytical theories are a valuable, computationally efficient tool for addressing general principles. LLPS of neutral homopolymers is quite well described by theory, but it has been a challenge to develop general theories for the LLPS of heteropolymers involving charge-charge interactions. Here, we present a theory that combines a random-phase-approximation treatment of polymer density fluctuations and an account of intrachain conformational heterogeneity based on renormalized Kuhn lengths to provide predictions of LLPS properties as a function of pH, salt, and charge patterning along the chain sequence. Advancing beyond more limited analytical approaches, our LLPS theory is applicable to a wide variety of charged sequences ranging from highly charged polyelectrolytes to neutral or nearly neutral polyampholytes. This theory should be useful in high-throughput screening of protein and other sequences for their LLPS propensities and can serve as a basis for more comprehensive theories that incorporate nonelectrostatic interactions. Experimental ramifications of our theory are discussed.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".