Elucidating key determinants of engineered scFv antibody in MMP-9 binding using high throughput screening and machine learning.
bioRxiv
; 2024 Jun 06.
Article
in En
| MEDLINE
| ID: mdl-38895413
ABSTRACT
An imbalance in matrix metalloproteinase-9 (MMP-9) regulation can lead to numerous diseases, including neurological disorders, cancer, and pre-term labor. Engineering single-chain antibody fragments (scFvs) Targeting MMP-9 to develop novel therapeutics for such diseases is desirable. We screened a synthetic scFv antibody library displayed on the yeast surface for binding improvement to MMP-9 using FACS (fluorescent-activated cell sorting). The scFv antibody clones isolated after FACS showed improvement in binding to MMP-9 compared to the endogenous inhibitor. To understand molecular determinants of binding between engineered scFv antibody variants and MMP-9, next-generation DNA sequencing, and computational protein structure analysis were used. Additionally, a deep-learning language model was trained on the synthetic library to predict the binding of scFv variants using their CDR-H3 sequences.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
BioRxiv
Year:
2024
Document type:
Article