期刊
MABS
卷 10, 期 8, 页码 1281-1290出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2018.1518887
关键词
Chemical stability; mass spectrometry; in silico modeling; protein structure; molecular modeling; structure property relationship; QSPR; algorithm; computer aided drug design; elastic network model
资金
- Genentech, Inc.
Monoclonal antibodies (mAbs) have become a major class of protein therapeutics that target a spectrum of diseases ranging from cancers to infectious diseases. Similar to any protein molecule, mAbs are susceptible to chemical modifications during the manufacturing process, long-term storage, and in vivo circulation that can impair their potency. One such modification is the oxidation of methionine residues. Chemical modifications that occur in the complementarity-determining regions (CDRs) of mAbs can lead to the abrogation of antigen binding and reduce the drug's potency and efficacy. Thus, it is highly desirable to identify and eliminate any chemically unstable residues in the CDRs during the therapeutic antibody discovery process. To provide increased throughput over experimental methods, we extracted features from the mAbs' sequences, structures, and dynamics, used random forests to identify important features and develop a quantitative and highly predictive in silico methionine oxidation model.
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