Computational Antibody Papers

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  • 2026-09-11

    Antibody maturation increases rigidity in protein-contacting regions and flexibility at glycan interfaces

    • molecular dynamics
    • MD simulation study showing that paratopes rigidify upon maturation.
    • Through over 8.5 milliseconds of molecular dynamics simulations across seven antibody lineages, the authors demonstrate that affinity maturation selectively tunes paratope dynamics by rigidifying protein-contacting regions while enhancing flexibility at glycan-contacting interfaces.
    • Global antibody flexibility displays no uniform trend across lineages. Intermediate antibodies often exhibit non-monotonic dynamic changes, localized conformational entropy is specifically adapted depending on the target antigen interface.
    • Variable region dynamics remain largely consistent regardless of whether the constant region is present or whether light chain isotypes (Kappa vs. Lambda) are swapped, proving that computational costs for all-atom simulations can be cut by at least half by simulating variable regions alone without sacrificing accuracy.

  • 2024-05-29

    Deciphering deamidation and isomerization in therapeutic proteins: Effect of neighboring residue

    • liabilities
    • molecular dynamics
    • quantum
    • Authors perform simulations of structure to create a classifier of ASP/ASN degradation.
    • They use the Adimab database of 131 therapeutics where degradation rates were studied.
    • They look at three metrics: D1) backbone dihedral conformation of the n + 1 residue, (D2) side-chain dihedral conformation of Asn/Asp residue, (D3) fraction of time the Asn/Asp residue remains solvent accessible.
    • The combined model achieves accuracy of around ~.85
    • The best accuracy is achieved on the backbone (D1) model, indicating that this might be the most important descriptor.
    • Citing the Adimab study: for instance, there were 27 deamidation sites with the hotspot NG sequence in the complementary-determining region (CDR), of which only 14 underwent deamidation. A similar trend was observed in the case of isomerization (16 of 44 DG sites isomerized).
    • They study the ASN/ASP degradation (isomerisation and deamidation) by looking at the proton affinity
    • Backbone secondary structure, side-chain rotamer conformation and solvent accessibility were found to be key molecular indicators of Asp isomerization and Asn deamidation