Steered molecular dynamics simulation as a post-process to optimize the iBRAB-designed Fab model.
iBRAB
Influenza A virus
SMD simulation
TAP
Therapeutic mAb
Journal
Journal of computer-aided molecular design
ISSN: 1573-4951
Titre abrégé: J Comput Aided Mol Des
Pays: Netherlands
ID NLM: 8710425
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
24
04
2024
accepted:
28
09
2024
medline:
24
10
2024
pubmed:
24
10
2024
entrez:
23
10
2024
Statut:
epublish
Résumé
Therapeutic monoclonal antibodies are an effective method of treating acute infectious diseases. However, knowing which of the produced antibodies in the vast number of human antibodies can cure the disease requires a long time and advanced technology. The previously introduced iBRAB method relies on studied antibodies to design a broad-spectrum antibody capable of neutralizing antigens of many different Influenza A viral strains. To evaluate the antigen-binding fragment as an applicable drug, the therapeutic antibody profiles providing guidelines collected from clinically staged therapeutic antibodies were used to access different measurements. Although the evaluated values were within an accepted range, the modification in the amino acid sequence is required for better properties. Thus, using the steered molecular dynamics (SMD) simulation to determine the binding capacity of amino acids in the functional region, the profile of interacted amino acids of Fab with the antigen was established for modified reference. As a result, the model was modified with amino acids elimination at positions 96-97 in the heavy chain and 26-27, 91, 96-97, and 102-103 in the light chain, which has better Therapeutic Antibody Profiler evaluations than the original designation. Thus again, SMD simulation is a promising computational approach for post-modification in rational drug design.
Identifiants
pubmed: 39443337
doi: 10.1007/s10822-024-00575-z
pii: 10.1007/s10822-024-00575-z
doi:
Substances chimiques
Immunoglobulin Fab Fragments
0
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
34Subventions
Organisme : Quỹ Đổi mới sáng tạo Vingroup
ID : VINIF.2020.TS
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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