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Cited 9 time in webofscience Cited 12 time in scopus
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Computer-based engineering of thermostabilized antibody fragments

Authors
Lee, JiwonDer, Bryan S.Karamitros, Christos S.Li, WenzongMarshall, Nicholas M.Lungu, Oana I.Miklos, Aleksandr E.Xu, JianqingKang, Tae HyunLee, Chang-HanTan, BingHughes, Randall A.Jung, Sang TaekIppolito, Gregory C.Gray, Jeffrey J.Zhang, YanKuhlman, BrianGeorgiou, GeorgeEllington, Andrew D.
Issue Date
Mar-2020
Publisher
WILEY
Keywords
antibody engineering; thermostable antibodies; Rosetta; scAb; scFv
Citation
AICHE Journal, v.66, no.3
Indexed
SCIE
SCOPUS
Journal Title
AICHE Journal
Volume
66
Number
3
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/942
DOI
10.1002/aic.16864
ISSN
0001-1541
1547-5905
Abstract
We used the molecular modeling program Rosetta to identify clusters of amino acid substitutions in antibody fragments (scFvs and scAbs) that improve global protein stability and resistance to thermal deactivation. Using this methodology, we increased the melting temperature (T-m) and resistance to heat treatment of an antibody fragment that binds to the Clostridium botulinum hemagglutinin protein (anti-HA33). Two designed antibody fragment variants with two amino acid replacement clusters, designed to stabilize local regions, were shown to have both higher T-m compared to the parental scFv and importantly to retain full antigen binding activity after 2 hr of incubation at 70 degrees C. The crystal structure of one thermostabilized scFv variants was solved at 1.6 angstrom and shown to be in close agreement with the RosettaAntibody model prediction.
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