The molecular reach of antibodies crucially underpins their viral neutralisation capacity.

Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study  >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces.

Aminomethylmorpholino Nucleosides as Novel Inhibitors of PARP1 and PARP2: Experimental and Molecular Modeling Analyses of Their Selectivity and Mechanism of Action.

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) play a key role in DNA repair. As major sensors of DNA damage, they are activated to produce poly(ADP-ribose). PARP1/PARP2 inhibitors have emerged as effective drugs for the treatment of cancers with BRCA deficiencies.

Divalent and multivalent cations control liquid-like assembly of poly(ADP-ribosyl)ated PARP1 into multimolecular associates in vitro.

The formation of nuclear biomolecular condensates is often associated with local accumulation of proteins at a site of DNA damage. The key role in the formation of DNA repair foci belongs to PARP1, which is a sensor of DNA damage and catalyzes the synthesis of poly(ADP-ribose) attracting repair factors. We show here that biogenic cations such as Mg, Ca, Mn, spermidine, or spermine can induce liquid-like assembly of poly(ADP-ribosyl)ated [PARylated] PARP1 into multimolecular associates (hereafter: self-assembly).

Covalent penicillin-protein conjugates elicit anti-drug antibodies that are clonally and functionally restricted.

Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates and their off-target side-conjugates have the potential to elicit antibodies, with implications for allergy and drug sequestration. Although β-lactam antibiotics are a drug class long associated with these immunological phenomena, the molecular underpinnings of off-target drug-protein conjugation and consequent drug-specific immune responses remain incomplete.