Downloads provided by UsageCountsHydrodynamic and Electrophoretic Properties of Trastuzumab/HER2 Extracellular Domain Complexes as Revealed by Experimental Techniques and Computational Simulations
Copyright policy ) Javier Ramos; Juan Francisco Vega; Victor Cruz; Eduardo Sanchez-Sanchez; Javier Cortes; Javier Martinez-Salazar;
Hydrodynamic and Electrophoretic Properties of Trastuzumab/HER2 Extracellular Domain Complexes as Revealed by Experimental Techniques and Computational Simulations
The 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.
Hydrodynamic properties, FENÓMENOS Y PROCESOS::fenómenos físicos::hidrodinámica, Receptor, ErbB-2, Static Electricity, PHENOMENA AND PROCESSES::Physical Phenomena::Hydrodynamics, :Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized::Trastuzumab [CHEMICALS AND DRUGS], Molecular dynamics, Trastuzumab/HER2 complexes, Article, :fenómenos físicos::hidrodinámica [FENÓMENOS Y PROCESOS], Antineoplastic Agents, Immunological, Humans, Dinàmica molecular, conformational fluctuations, Binding Sites, Hidrodinàmica, :técnicas de investigación::modelos teóricos::modelos moleculares::simulación de acoplamiento molecular [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Trastuzumab, molecular dynamics, Càncer - Simulació per ordinador, Molecular Docking Simulation, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking Simulation, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::modelos teóricos::modelos moleculares::simulación de acoplamiento molecular, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized::Trastuzumab, hydrodynamic properties, Hydrodynamics, :Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking Simulation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados::trastuzumab, :aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados::trastuzumab [COMPUESTOS QUÍMICOS Y DROGAS], Conformational fluctuations, :Physical Phenomena::Hydrodynamics [PHENOMENA AND PROCESSES], Protein Binding
Hydrodynamic properties, FENÓMENOS Y PROCESOS::fenómenos físicos::hidrodinámica, Receptor, ErbB-2, Static Electricity, PHENOMENA AND PROCESSES::Physical Phenomena::Hydrodynamics, :Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized::Trastuzumab [CHEMICALS AND DRUGS], Molecular dynamics, Trastuzumab/HER2 complexes, Article, :fenómenos físicos::hidrodinámica [FENÓMENOS Y PROCESOS], Antineoplastic Agents, Immunological, Humans, Dinàmica molecular, conformational fluctuations, Binding Sites, Hidrodinàmica, :técnicas de investigación::modelos teóricos::modelos moleculares::simulación de acoplamiento molecular [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Trastuzumab, molecular dynamics, Càncer - Simulació per ordinador, Molecular Docking Simulation, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking Simulation, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::modelos teóricos::modelos moleculares::simulación de acoplamiento molecular, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized::Trastuzumab, hydrodynamic properties, Hydrodynamics, :Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking Simulation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados::trastuzumab, :aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados::trastuzumab [COMPUESTOS QUÍMICOS Y DROGAS], Conformational fluctuations, :Physical Phenomena::Hydrodynamics [PHENOMENA AND PROCESSES], Protein Binding
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