id:"swepub:oai:DiVA.org:liu-128265"
Search: id:"swepub:oai:DiVA.org:liu-128265" > Conformational flex...
- 1 of 1
- Previous record
- Next record
- To hitlist
- Franco-Gonzalez, Juan FelipeMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (author)
Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody complex as revealed by molecular dynamics and principal component analysis.
- Article/chapterEnglish2013
Publisher, publication year, extent ...
- 2012-11-17
- Springer Science and Business Media LLC,2013
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:liu-128265
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-128265URI
- https://doi.org/10.1007/s00894-012-1661-3DOI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- Human epidermal growth factor receptor 2 (ErbB2) is a transmembrane oncoprotein that is over expressed in breast cancer. A successful therapeutic treatment is a monoclonal antibody called trastuzumab which interacts with the ErbB2 extracellular domain (ErbB2-ECD). A better understanding of the detailed structure of the receptor-antibody interaction is indeed of prime interest for the design of more effective anticancer therapies. In order to discuss the flexibility of the complex ErbB2-ECD/trastuzumab, we present, in this study, a multi-nanosecond molecular dynamics simulation (MD) together with an analysis of fluctuations, through a principal component analysis (PCA) of this system. Previous to this step and in order to validate the simulations, we have performed a detailed analysis of the variable antibody domain interactions with the extracellular domain IV of ErbB2. This structure has been statically elucidated by x-ray studies. Indeed, the simulation results are in excellent agreement with the available experimental information during the full trajectory. The PCA shows eigenvector fluctuations resulting in a hinge motion in which domain II and C(H) domains approach each other. This move is likely stabilized by the formation of H-bonds and salt bridge interactions between residues of the dimerization arm in the domain II and trastuzumab residues located in the C(H) domain. Finally, we discuss the flexibility of the MD/PCA model in relation with the static x-ray structure. A movement of the antibody toward the dimerization domain of the ErbB2 receptor is reported for the first time. This finding could have important consequences on the biological action of the monoclonal antibody.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
- Cruz, Victor LMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (author)
- Ramos, JavierMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (author)
- Martínez-Salazar, JavierMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (author)
- Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (creator_code:org_t)
Related titles
- In:Journal of Molecular Modeling: Springer Science and Business Media LLC19:3, s. 1227-12361610-29400948-5023
Internet link
Find in a library
- Journal of Molecular Modeling (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Franco-Gonzalez, ...
- Cruz, Victor L
- Ramos, Javier
- Martínez-Salazar ...
- About the subject
-
- NATURAL SCIENCES
- NATURAL SCIENCES
- and Biological Scien ...
- and Biophysics
- Articles in the publication
- Journal of Molec ...
- By the university
- Linköping University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
