scholarly journals Effect of double mutations T790M/L858R on conformation and drug-resistant mechanism of epidermal growth factor receptor explored by molecular dynamics simulations

RSC Advances ◽  
2018 ◽  
Vol 8 (70) ◽  
pp. 39797-39810 ◽  
Author(s):  
Fangfang Yan ◽  
Xinguo Liu ◽  
Shaolong Zhang ◽  
Jing Su ◽  
Qinggang Zhang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Epidermal Growth Factor Receptor ◽  
Decomposition Method ◽  
Growth Factor Receptor ◽  
Drug Resistant ◽  
Energy Decomposition ◽  
Free Energy Decomposition ◽  
Epidermal Growth ◽  
Dynamics Simulations

The MM-GBSA method coupled with residue-based free energy decomposition method was performed to explore drug-resistant mechanisms of the mutated EGFR.

scholarly journals Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S

2019 ◽  
Vol 10 (46) ◽  
pp. 10789-10801 ◽  
Author(s):  
Jonas Lategahn ◽  
Marina Keul ◽  
Philip Klövekorn ◽  
Hannah L. Tumbrink ◽  
Janina Niggenaber ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Binding Mode ◽  
Drug Resistant ◽  
X Ray ◽  
Covalent Inhibitors ◽  
Epidermal Growth ◽  
Resistant Mutants ◽  
Insight Into ◽  
Egfr T790m

We present inhibitors of drug resistant mutants of EGFR including T790M and C797S. In addition, we present the first X-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR to gain insight into their binding mode.

scholarly journals Structure-Based Drug Design Studies Toward the Discovery of Novel Chalcone Derivatives as Potential Epidermal Growth Factor Receptor (EGFR) Inhibitors

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3203 ◽  
Author(s):  
Menier Al-Anazi ◽  
Belal Al-Najjar ◽  
Melati Khairuddean
Keyword(s):  
Molecular Dynamics ◽  
Epidermal Growth Factor Receptor ◽  
Molecular Dynamics Simulation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Active Site ◽  
Growth Factor Receptor ◽  
Dynamics Simulation ◽  
Chalcone Derivatives ◽  
Epidermal Growth

Human Epidermal Growth Factor Receptor-1 (EGFR), a transmembrane tyrosine kinase receptor (RTK), has been associated with several types of cancer, including breast, lung, ovarian, and anal cancers. Thus, the receptor was targeted by a variety of therapeutic approaches for cancer treatments. A series of chalcone derivatives are among the most highly potent and selective inhibitors of EGFR described to date. A series of chalcone derivatives were proposed in this study to investigate the intermolecular interactions in the active site utilizing molecular docking and molecular dynamics simulations. After a careful analysis of docking results, compounds 1a and 1d were chosen for molecular dynamics simulation study. Extensive hydrogen bond analysis throughout 7 ns molecular dynamics simulation revealed the ability of compounds 1a and 1d to retain the essential interactions needed for the inhibition, especially MET 93. Finally, MM-GBSA calculations highlight on the capability of the ligands to bind strongly within the active site with binding energies of −44.04 and −56.6 kcal/mol for compounds 1a and 1d, respectively. Compound 1d showed to have a close binding energy with TAK-285 (−66.17 kcal/mol), which indicates a high chance for compound 1d to exhibit inhibitory activity, thus recommending to synthesis it to test its biological activity. It is anticipated that the findings reported here may provide very useful information for designing effective drugs for the treatment of EGFR-related cancer disease.

scholarly journals A Brief History of Single-Particle Tracking of the Epidermal Growth Factor Receptor

2019 ◽  
Vol 2 (1) ◽  
pp. 12 ◽  
Author(s):  
David T. Clarke ◽  
Marisa L. Martin-Fernandez
Keyword(s):  
Molecular Dynamics ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Particle Tracking ◽  
Single Particle ◽  
Growth Factor Receptor ◽  
Single Particle Tracking ◽  
Epidermal Growth ◽  
And Function

Single-particle tracking (SPT) has been used and developed over the last 25 years as a method to investigate molecular dynamics, structure, interactions, and function in the cellular context. SPT is able to show how fast and how far individual molecules move, identify different dynamic populations, measure the duration and strength of intermolecular interactions, and map out structures on the nanoscale in cells. In combination with other techniques such as macromolecular crystallography and molecular dynamics simulation, it allows us to build models of complex structures, and develop and test hypotheses of how these complexes perform their biological roles in health as well as in disease states. Here, we use the example of the epidermal growth factor receptor (EGFR), which has been studied extensively by SPT, demonstrating how the method has been used to increase our understanding of the receptor’s organization and function, including its interaction with the plasma membrane, its activation, clustering, and oligomerization, and the role of other receptors and endocytosis. The examples shown demonstrate how SPT might be employed in the investigation of other biomolecules and systems.

Sign in / Sign up

Export Citation Format

Share Document