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Chemical biology

Calixarene docks dimethyllysine on lysozyme

McGovern RE, Snarr BD, Lyons JA, et al. · Chemical science · 2015

Open access · cc by · source: Europe PMC

p-Sulfonatocalix[4]arene selectively encapsulates Lys116-Me2 on dimethylated lysozyme, mimicking an aromatic cage.

Study at a glance

Design
Other — Crystal and NMR study of p-sulfonatocalix[4]arene bound to dimethylated lysozyme lysines
N
Protein–small-molecule structural study — no cohort N
Population
Dimethylated hen egg-white lysozyme with sclx4
Outcome
Site-selective Lys-Me2 encapsulation by the calixarene

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Lys116-Me2 is encapsulated in the calixarene; NMR shows a large upfield NεMe shift; accessibility and nearby Arg/Asn contacts explain selectivity versus other lysines.

Methodology

Authors dimethylated hen lysozyme, solved sclx4 co-crystal structures, used 1H/13C NMR chemical shifts, and ran short MD at each Lys-Me2 site.

Limitations

No histone-tail co-crystal; MM-PBSA could not rank sites; precipitation limited solution stoichiometry.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • MD plus docking can design peptides that then meet a wet IC₅₀, which is a stronger claim than MD that cannot rank sites. SARS-CoV-2 Mpro peptides p12–p16 have IC₅₀ 3.11–5.36 μM; at 8-fold excess they cut s01 depletion from >98% to 70–95%; the ion-pair dyad lies 28.5 kJ mol⁻¹ above the neutral state. On dimethylated lysozyme, short MD at each Lys-Me₂ and a crystal of sclx4 encapsulating Lys116-Me₂ still left MM-PBSA unable to rank sites; precipitation limited solution stoichiometry.

    Evidence for the claim as stated.

  • A short classical MD on a crystal pose can fail at ranking, while a neural-network AIMD-quality trajectory can propose a path. MM-PBSA could not rank lysozyme Lys-Me₂ sites; the Au(100) NNP metadynamics did propose an associative 0.3 eV ORR path — still without cations or bias. Success is Hamiltonian- and question-specific, not a property of 'having run MD'.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

  • Scope difference — different assays, populations, or outcomes

    A short classical MD on a crystal pose can fail at ranking, while a neural-network AIMD-quality trajectory can propose a path. MM-PBSA could not rank lysozyme Lys-Me₂ sites; the Au(100) NNP metadynamics did propose an associative 0.3 eV ORR path — still without cations or bias. Success is Hamiltonian- and question-specific, not a property of 'having run MD'.

    Also on this tension

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Same topic cluster — not a recommendation engine.