ArticleBiophysical journal2009
Atomistic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study.
Article in Biophysical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Advances in Small-molecule Dual Inhibitors Targeting EGFR and HER2 Receptors as Anti-cancer Agents.Current medicinal chemistry · 2025Review
- Acute amivantamab-induced myocardial injury in a patient with epidermal growth factor receptor-mutant lung cancer: a first case report.Frontiers in oncology · 2025Article
- Molecular dynamics simulations of the conformational plasticity in the active pocket of salt-inducible kinase 2 (SIK2) multi-state binding with bosutinib.Computational and structural biotechnology journal · 2022Article
- Recombinant immunotoxins development for HER2-based targeted cancer therapies.Cancer cell international · 2021Review
- Computational algorithms for in silico profiling of activating mutations in cancer.Cellular and molecular life sciences : CMLS · 2019Review
- Structural investigations on mechanism of lapatinib resistance caused by HER-2 mutants.PloS one · 2018Article
- Analysis of different HER-2 mutations in breast cancer progression and drug resistance.Journal of cellular and molecular medicine · 2015Review
- 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.Journal of computer-aided molecular design · 2014Article
- Article
- Molecular modeling of ErbB4/HER4 kinase in the context of the HER4 signaling network helps rationalize the effects of clinically identified HER4 somatic mutations on the cell phenotype.Biotechnology journal · 2013Article
- Personalizing therapies for gastric cancer: molecular mechanisms and novel targeted therapies.World journal of gastroenterology · 2013Review
- Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface.The Journal of biological chemistry · 2013Article
- Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody complex as revealed by molecular dynamics and principal component analysis.Journal of molecular modeling · 2013Article
- Structural systems biology and multiscale signaling models.Annals of biomedical engineering · 2012Review
- Medicinal chemistry for 2020.Future medicinal chemistry · 2011Article
- Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases.PLoS computational biology · 2011Article
- Multiscale cancer modeling.Annual review of biomedical engineering · 2011Review
- Carboxyl-group footprinting maps the dimerization interface and phosphorylation-induced conformational changes of a membrane-associated tyrosine kinase.Molecular & cellular proteomics : MCP · 2011Article
- A multiscale modeling approach to investigate molecular mechanisms of pseudokinase activation and drug resistance in the HER3/ErbB3 receptor tyrosine kinase signaling network.Molecular bioSystems · 2011Article
- Molecular dynamics analysis of conserved hydrophobic and hydrophilic bond-interaction networks in ErbB family kinases.The Biochemical journal · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2 (ErbB2/Neu) is a receptor tyrosine kinase belonging to the epidermal growth factor receptor (EGFR)/ErbB family and is overexpressed in 20-30% of human breast cancers. Although several crystal structures of ErbB kinases have been solved, the precise mechanism of HER2 activation remains unknown, and it has been suggested that HER2 is unique in its requirement for phosphorylation of Y877, a key tyrosine residue located in the activation loop. To elucidate mechanistic details of kinase domain regulation, we performed molecular dynamics simulations of a homology-modeled HER2 kinase structure in active and inactive conformations. Principal component analysis of the atomistic fluctuations reveals a tight coupling between the activation loop and catalytic loop that may contribute to alignment of residues required for catalysis in the active kinase. The free energy perturbation method is also employed to predict a role for phosphorylated Y877 in stabilizing the kinase conformations. Finally, simulation results are presented for a HER2/EGFR heterodimer and reveal that the dimeric interface induces a rearrangement of the alphaC helix toward the active conformation. Elucidation of the molecular regulatory mechanisms in HER2 will help establish structure-function relationships in the wild-type kinase, as well as predict mutations with a propensity for constitutive activation in HER2-mediated cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.