All-atom modeling of methacrylate-based multi-modal chromatography resins for Langmuir constant prediction of peptides.
J Chromatogr A
; 1730: 465089, 2024 Aug 16.
Article
in En
| MEDLINE
| ID: mdl-38879977
ABSTRACT
In downstream processing, the intricate nature of the interactions between biomolecules and adsorbent materials presents a significant challenge in the prediction of their binding and elution behaviors. This complexity is further heightened in multi-modal chromatography (MMC), which employs two distinct binding mechanisms. To gain a deeper understanding of the involved interactions, simulating the adsorption of biomolecules on resin surfaces is a focal point of ongoing research. However, previous studies often simplified the adsorbent surface, modeling it as a flat or slightly curved plane without including a realistic backbone structure. Here, we introduce and validate two novel workflows aimed at predicting peptide binding behaviors in MMC, specifically targeting methacrylate-based resins. Our first achievement was the development of an all-atom model of a commercial MMC resin surface, incorporating its polymethacrylic backbone. Furthermore, we established and tested a workflow for rapid calculations of binding free energies (ΔG) with 10 linear peptides as target molecules. These ΔG calculations were effectively used to predict Langmuir constants, achieving a high coefficient of determination (R²) of 0.96. In subsequent benchmarking tests, our model outperformed established, simpler resin surface models in terms of predictive capabilities.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Methacrylates
Language:
En
Journal:
J Chromatogr A
Year:
2024
Document type:
Article
Affiliation country:
Germany
Country of publication:
Netherlands