Characterization of the conformational ensemble from bioactive N-acylhydrazone derivatives

Journal of Molecular Graphics & Modelling
L Pol-FachinH Verli

Abstract

The search for bioactive conformations from prototypes is mostly referenced on crystallographic ligand-receptor complexes, in which the molecule conformation is already caged inside its binding site. However, the complexation process is a thermodynamic event depending on both complexed and uncomplexed states. As ligand affinity originates from such equilibrium, the development of novel computational models capable of supplying data on ligand dynamics in biological solutions is potentially applicable in more efficient methods for prediction of compounds binding and affinity. In this context, the current work employs a series of molecular dynamics simulations on three N-acylhydrazone derivatives, already shown to present promising cardioinotropic and vasodilatory activities, in order to obtain a precise characterization of each compound conformational ensemble in aqueous solutions, instead of a single minimum energy conformation. Consequently, we were able to observe the influence of each functional group of the studied molecules on the conformation of the entire compounds and thus on the exposure of functional groups that might potentially bind to target receptors. Additionally, the differences between the molecules conformation...Continue Reading

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Citations

Mar 26, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Conrado PedebosHugo Verli
Sep 13, 2014·Expert Opinion on Therapeutic Patents·Rodolfo do Couto MaiaCarlos Alberto Manssour Fraga
Jan 21, 2017·ACS Medicinal Chemistry Letters·Jolanta DyniewiczAndrzej W Lipkowski

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