Assessment of new anti-HER2 ligands using combined docking, QM/MM scoring and MD simulation

Ahmed M.; Sadek M.M.; Serrya R.A.; Kafafy A.-H.N.; Abouzid K.A.; Wang F.

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Assessment of new anti-HER2 ligands using combined docking, QM/MM scoring and MD simulation

Ahmed M.; Sadek M.M.; Serrya R.A.; Kafafy A.-H.N.; Abouzid K.A.; Wang F.

Full Text link: https://t.ly/BXJPn

Date issued: 2013

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Doi: https://doi.org/10.1016/j.jmgm.2012.12.001 PubMed ID 23353584

Series Info: Journal of Molecular Graphics and Modelling
40

Type: Article

Keywords: AMBER , HER2 , Molecular dynamics , Protein kinase , QM/MM scoring , Active compounds , Active site , Anticancer drug , Chemotherapeutic agents , HER2 , Human epidermal growth factor , Induced fit , MD simulation , Protein kinase , QM/MM scoring , Scoring functions , Stability parameters , Amber , Computer simulation , Proteins , Molecular dynamics , epidermal growth factor receptor 2 , epidermal growth factor receptor kinase inhibitor , article , drug activity , drug binding , drug stability , drug structure , drug synthesis , molecular docking , molecular dynamics , priority journal , scoring system , Antineoplastic Agents , Drug Design , Humans , Ligands , Models, Molecular , Protein Binding , Quantum Theory , Receptor, erbB-2 , Structure-Activity Relationship

Abstract:

In the development of new anti-cancer drugs to tackle the problem of resistance to current chemotherapeutic agents, a new series of anti-HER2 (human epidermal growth factor receptors 2) agents has been synthesized and investigated using different computational methods. Although non-selective, the most active inhibitor in the new series shows higher activity toward HER2 than EGFR. The induced fit docking protocol (IFD) is performed to find possible binding poses of the new inhibitors in the active site of the HER2 receptor. Molecular dynamic simulations of the inhibitor-protein complexes for the two most active compounds from the new series are carried out. Simulations stability is checked using different stability parameters. Different scoring functions are employed. � 2012 Elsevier Inc.