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Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab-Fab antibody in a lipid bilayer model using Martini coarse-grained force field

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Abstract

Coarse grained (CG) modeling has been applied to study the influence of the Trastuzumab monoclonal antibody on the structure and dynamics of the full ErbB2 receptor dimer, including the lipid bilayer. The usage of CG models to study such complexes is almost mandatory, at present, due to the large size of the whole system. We will show that the Martini model performs satisfactorily well, giving results well-matched with those obtained by atomistic models as well as with the experimental information existing on homolog receptors. For example, the extra and intracellular domains approach the bilayer surface in both the monomer and dimer cases. The Trastuzumab-Fab hinders the interaction of the receptors with the lipid bilayer. Another interesting effect of the antibody is the disruption of the antiparallel arrangement of the juxtamembrane segments in the dimer case. These findings might help to understand the effect of the antibody on the receptor bioactivity.

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Acknowledgments

This study received financial support from the CICYT (projects MAT2009-12364 and MAT2012-36341). J.R. thanks to MINECO (Ministerio de Economía y Competitividad) the financial support through the Ramón y Cajal program, contract RYC-2011-09585. The authors thank the staff of the SGAI-CSIC (Secretaria General Adjunta de Informática) for technical support and computer time for the simulations. We are also grateful to Prof. Bagossi for sharing his atomistic model in PDB format.

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Authors and Affiliations

  1. Biophym, Macromolecular Physics Department, Instituto de Estructura de la Materia, CSIC, Serrano 113-bis, 28006, Madrid, Spain

    Juan Felipe Franco-Gonzalez, Javier Ramos, Victor L. Cruz & Javier Martinez-Salazar

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  1. Juan Felipe Franco-Gonzalez
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  2. Javier Ramos
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  3. Victor L. Cruz
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  4. Javier Martinez-Salazar
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Correspondence to Victor L. Cruz.

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Franco-Gonzalez, J.F., Ramos, J., Cruz, V.L. et al. Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab-Fab antibody in a lipid bilayer model using Martini coarse-grained force field. J Comput Aided Mol Des 28, 1093–1107 (2014). https://doi.org/10.1007/s10822-014-9787-2

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  • DOI: https://doi.org/10.1007/s10822-014-9787-2

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