Mesoscale Modeling of a Nucleosome-Binding Antibody (PL2-6): Mono- vs. Bivalent Chromatin Complexes
Bibliographic record
Abstract
ABSTRACT Visualizing chromatin adjacent to the nuclear envelope (denoted “epichromatin”) by in vitro immunostaining with a bivalent nucleosome-binding antibody (termed monoclonal antibody PL2-6) has suggested a distinct and conserved chromatin structure. Moreover, different staining patterns for chromatin complexed with the monovalent “Fab” fragment of PL2-6, compared to the bivalent form, point to distinct binding interactions. To help interpret antibody/chromatin interactions and these differential binding modes, we incorporate coarse-grained PL2-6 antibody modeling into our mesoscale chromatin model and analyze interactions and fiber structures for the antibody/chromatin complexes in open and condensed chromatin, with and without linker histone H1 (LH). Despite minimal and transient interactions at physiological salt, we capture differential binding for monomer and dimer antibody forms to open fibers, with much more intense interactions in the bivalent antibody/chromatin complex. For these open “zigzag” fiber morphologies, differences result from antibody competition for peptide tail contacts with internal chromatin fiber components (nucleosome core and linker DNA). Antibody competition results in dramatic conformational and energetic differences among monovalent , bivalent , and free chromatin systems in the parental linker DNA / tail interactions. These differences in binding modes and changes in internal fiber structure, driven by conformational entropy gains, help interpret the differential staining patterns for the monovalent versus bivalent antibody/chromatin complexes. More generally, such dynamic interactions which depend on the complex internal structure and self-interactions of the chromatin fiber have broader implications to other systems that bind to chromatin, such as linker histones and remodeling proteins. STATEMENT OF SIGNIFICANCE Using mesoscale modeling, we help interpret differential binding modes for antibody/chromatin interactions to elucidate the structural details of “epichromatin” (chromatin adjacent to the nuclear envelope), which had been visualized to produce different staining patterns for monovalent and bivalent forms of the PL2-6 antibody. To our knowledge, this is the first application of such a coarse-grained computational antibody model to probe chromatin structure and mechanisms of antibody/chromatin binding. Our work emphasizes how antibody units compete with native internal chromatin fiber units (histone tails, nucleosome core, and linker DNA) for fiber-stabilizing interactions and thereby drive differential antibody binding for open zigzag chromatin fibers. Such competition, which dynamically alters internal chromatin structure upon binding, could be relevant to other chromatin binding mechanisms such as those involving linker histones or chromatin remodeling proteins.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".