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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorRamos, Javier
dc.contributor.authorVega, Juan Francisco
dc.contributor.authorCruz, Victor
dc.contributor.authorSanchez-Sanchez, Eduardo
dc.contributor.authorCortés Castan, Javier
dc.contributor.authorMartinez-Salazar, Javier
dc.date.accessioned2021-03-19T09:49:05Z
dc.date.available2021-03-19T09:49:05Z
dc.date.issued2019-03-01
dc.identifier.citationRamos J, Vega JF, Cruz V, Sanchez-Sanchez E, Cortes J, Martinez-Salazar J. Hydrodynamic and Electrophoretic Properties of Trastuzumab/HER2 Extracellular Domain Complexes as Revealed by Experimental Techniques and Computational Simulations. Int J Mol Sci. 2019 Mar 1;20(5):1076.
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/11351/5776
dc.descriptionTrastuzumab / HER2 complexes; Hydrodynamic properties; Molecular dynamics
dc.description.abstractThe combination of hydrodynamic and electrophoretic experiments and computer simulations is a powerful approach to study the interaction between proteins. In this work, we present hydrodynamic and electrophoretic experiments in an aqueous solution along with molecular dynamics and hydrodynamic modeling to monitor and compute biophysical properties of the interactions between the extracellular domain of the HER2 protein (eHER2) and the monoclonal antibody trastuzumab (TZM). The importance of this system relies on the fact that the overexpression of HER2 protein is related with the poor prognosis breast cancers (HER2++ positives), while the TZM is a monoclonal antibody for the treatment of this cancer. We have found and characterized two different complexes between the TZM and eHER2 proteins (1:1 and 1:2 TZM:eHER2 complexes). The conformational features of these complexes regulate their hydrodynamic and electrostatic properties. Thus, the results indicate a high degree of molecular flexibility in the systems that ultimately leads to higher values of the intrinsic viscosity, as well as lower values of diffusion coefficient than those expected for simple globular proteins. A highly asymmetric charge distribution is detected for the monovalent complex (1:1 complex), which has strong implications in correlations between the experimental electrophoretic mobility and the modeled net charge. In order to understand the dynamics of these systems and the role of the specific domains involved, it is essential to find biophysical correlations between dynamics, macroscopic transport and electrostatic properties. The results should be of general interest for researchers working in this area.
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesInternational Journal of Molecular Sciences;20(5)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectDinàmica molecular
dc.subjectCàncer - Simulació per ordinador
dc.subjectHidrodinàmica
dc.subject.meshMolecular Docking Simulation
dc.subject.meshHydrodynamics
dc.subject.meshTrastuzumab
dc.titleHydrodynamic and Electrophoretic Properties of Trastuzumab/HER2 Extracellular Domain Complexes as Revealed by Experimental Techniques and Computational Simulations
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3390/ijms20051076
dc.subject.decssimulación de acoplamiento molecular
dc.subject.decshidrodinámica
dc.subject.decstrastuzumab
dc.relation.publishversionhttps://www.mdpi.com/1422-0067/20/5/1076
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Ramos J, Vega JF, Cruz V, Sanchez-Sanchez E, Martinez-Salazar J] BIOPHYM, Department of Macromolecular Physics, Instituto de Estructura de la Materia, IEM-CSIC, Madrid, Spain. [Cortes J] Ramón y Cajal University Hospital, Madrid, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.identifier.pmid30832287
dc.identifier.wos000462542300075
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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