Llamanade: An open-source computational pipeline for robust nanobody humanization.
Structure
; 30(3): 418-429.e3, 2022 03 03.
Article
in English
| MEDLINE | ID: covidwho-1559760
ABSTRACT
Nanobodies (Nbs) have emerged as a promising class of biologics. Despite having marked physicochemical properties, Nbs are derived from camelids and may require humanization to improve translational potentials. By systematically analyzing the sequence and structural properties of Nbs, we found substantial framework diversities and revealed the key differences between Nbs and human immunoglobulin G antibodies. We identified conserved residues that may contribute to enhanced solubility, structural stability, and antigen binding, providing insights into Nb humanization. Based on big data analysis, we developed "Llamanade," an open-source software to facilitate rational humanization of Nbs. Using sequence as input, Llamanade can rapidly extract sequence features, model structures, and optimize solutions to humanize Nbs. Finally, we used Llamanade to successfully humanize a cohort of structurally diverse and potent SARS-CoV-2 neutralizing Nbs. Llamanade is freely available and will be easily accessible on a server to support the development of therapeutic Nbs into safe and effective trials.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Monoclonal, Humanized
/
Single-Domain Antibodies
/
SARS-CoV-2
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Language:
English
Journal:
Structure
Journal subject:
Molecular Biology
/
Biochemistry
/
Biotechnology
Year:
2022
Document Type:
Article
Affiliation country:
J.str.2021.11.006
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