Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody complex as revealed by molecular dynamics and principal component analysis.

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Sökning: id:"swepub:oai:DiVA.org:liu-128265" > Conformational flex...

1 av 1
Föregående post
Nästa post
Till träfflistan

Franco-Gonzalez, Juan FelipeMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (författare)

Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody complex as revealed by molecular dynamics and principal component analysis.

Artikel/kapitelEngelska2013

Förlag, utgivningsår, omfång ...

2012-11-17
Springer Science and Business Media LLC,2013
printrdacarrier

Nummerbeteckningar

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

Kompletterande språkuppgifter

Språk:engelska
Sammanfattning på:engelska

Ingår i deldatabas

SwePubSwePub

Klassifikation

Ämneskategori:ref swepub-contenttype
Ämneskategori:art swepub-publicationtype

Anmärkningar

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.

Ämnesord och genrebeteckningar

NATURVETENSKAP Biologi Biofysik hsv//swe
NATURAL SCIENCES Biological Sciences Biophysics hsv//eng

Biuppslag (personer, institutioner, konferenser, titlar ...)

Cruz, Victor LMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (författare)
Ramos, JavierMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (författare)
Martínez-Salazar, JavierMacromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (författare)
Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Madrid, Spain (creator_code:org_t)

Sammanhörande titlar

Ingår i:Journal of Molecular Modeling: Springer Science and Business Media LLC19:3, s. 1227-12361610-29400948-5023

Internetlänk

Hitta via bibliotek

Journal of Molecular Modeling (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

1 av 1
Föregående post
Nästa post
Till träfflistan

Hitta mer i SwePub

Av författaren/redakt...: Franco-Gonzalez, ...; Cruz, Victor L; Ramos, Javier; Martínez-Salazar ...

Om ämnet

NATURVETENSKAP: NATURVETENSKAP; och Biologi; och Biofysik

Artiklar i publikationen: Journal of Molec ...

Av lärosätet: Linköpings universitet

Sök utanför SwePub

Sök vidare i:: Google; 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.

LIBRIS.kb.se