Force field study of the interaction between dihydropyridine derivatives and a synthetic Ca²⁺ channel peptide

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• 作者：Ramusino ; Marina Cotta ; Varì ; Maria Rosaria
• 关键词：Dihydropyridine derivatives ; Calcium-channel antagonists ; Synthetic Ca²⁺ channel peptide ; Docking study ; Force field computational methods
• 刊名：Journal of Molecular Structure: THEOCHEM
• 出版年：2003
• 出版时间：April 4, 2003
• 年：2003
• 卷：623
• 期：1-3
• 页码：87-93
• 全文大小：160 K

文摘

We investigated the binding mode of a set of dihydropyridine calcium channel antagonists to a synthetic Ca²⁺ channel peptide with a force field computational procedure. Different conformers of each ligand were docked into the synthetic channel peptide to take into account that the ligand conformation at the receptor site may not correspond to the most stable one of the isolated molecule. In the docking procedure the molecular structure of the Ca²⁺ channel was kept rigid while the ligands were assumed to be flexible. The ranking of the computed interaction energies correlated with the biological activity data (expressed as the IC₅₀ values for the blockage of Ca²⁺ induced contraction of K⁺ depolarized rat aorta). The computational procedure also discriminated between the S and R enantiomers of the ligand amlodipine, predicting a stronger interaction of the former with the Ca²⁺ channel model.