{"title":"Inhibition of human epidermal growth factor receptor-2 protein by some alkaloid inhibitors","authors":"","doi":"10.1016/j.molliq.2024.125608","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Human Epidermal Growth Factor Receptor-2 (HER2), a transmembrane tyrosine kinase receptor, has been associated with several types of cancer, including breast, lung, ovarian, etc. Therefore, this receptor is targeted by a variety of therapeutic approaches for cancer treatments. The alkaloid and lead compounds are among the selective and potent HER2 inhibitors that have been reported so far.</p></div><div><h3>Methods</h3><p>The present work involves molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations on alkaloid and lead compounds as HER2 inhibitors.</p></div><div><h3>Significant findings</h3><p>The docking results expressed that the alkaloids mainly interacted with Cys805, Val734, and Ala751 residues of HER2 protein. The MD simulation outcomes represented that all the complexes have adequate dynamic stability and flexibility based on the root mean square deviation, root mean square fluctuation, and radius of gyration. Furthermore, it is found that the strongest HER2 − ligand interaction belongs to the nocamycin I (NOI, ΔG<sub>bind</sub> = -12.84 kcal mol<sup>−1</sup>) molecule. The DFT calculations showed that electron density and the second − order perturbation stabilization energy values for HER2 − NOI interactions are higher than the other complexes. The molecular docking, MD simulation, and DFT calculation results are all in agreement and complementary. It is expected that the results obtained here can present very helpful information for the design of efficacious inhibitors for the treatment of HER2 − related cancer disease.</p></div>","PeriodicalId":371,"journal":{"name":"Journal of Molecular Liquids","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Liquids","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167732224016672","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Human Epidermal Growth Factor Receptor-2 (HER2), a transmembrane tyrosine kinase receptor, has been associated with several types of cancer, including breast, lung, ovarian, etc. Therefore, this receptor is targeted by a variety of therapeutic approaches for cancer treatments. The alkaloid and lead compounds are among the selective and potent HER2 inhibitors that have been reported so far.
Methods
The present work involves molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations on alkaloid and lead compounds as HER2 inhibitors.
Significant findings
The docking results expressed that the alkaloids mainly interacted with Cys805, Val734, and Ala751 residues of HER2 protein. The MD simulation outcomes represented that all the complexes have adequate dynamic stability and flexibility based on the root mean square deviation, root mean square fluctuation, and radius of gyration. Furthermore, it is found that the strongest HER2 − ligand interaction belongs to the nocamycin I (NOI, ΔGbind = -12.84 kcal mol−1) molecule. The DFT calculations showed that electron density and the second − order perturbation stabilization energy values for HER2 − NOI interactions are higher than the other complexes. The molecular docking, MD simulation, and DFT calculation results are all in agreement and complementary. It is expected that the results obtained here can present very helpful information for the design of efficacious inhibitors for the treatment of HER2 − related cancer disease.
期刊介绍:
The journal includes papers in the following areas:
– Simple organic liquids and mixtures
– Ionic liquids
– Surfactant solutions (including micelles and vesicles) and liquid interfaces
– Colloidal solutions and nanoparticles
– Thermotropic and lyotropic liquid crystals
– Ferrofluids
– Water, aqueous solutions and other hydrogen-bonded liquids
– Lubricants, polymer solutions and melts
– Molten metals and salts
– Phase transitions and critical phenomena in liquids and confined fluids
– Self assembly in complex liquids.– Biomolecules in solution
The emphasis is on the molecular (or microscopic) understanding of particular liquids or liquid systems, especially concerning structure, dynamics and intermolecular forces. The experimental techniques used may include:
– Conventional spectroscopy (mid-IR and far-IR, Raman, NMR, etc.)
– Non-linear optics and time resolved spectroscopy (psec, fsec, asec, ISRS, etc.)
– Light scattering (Rayleigh, Brillouin, PCS, etc.)
– Dielectric relaxation
– X-ray and neutron scattering and diffraction.
Experimental studies, computer simulations (MD or MC) and analytical theory will be considered for publication; papers just reporting experimental results that do not contribute to the understanding of the fundamentals of molecular and ionic liquids will not be accepted. Only papers of a non-routine nature and advancing the field will be considered for publication.