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Computer-based techniques for lead identification and optimization II: Advanced search methods

  • Antonio Lupia , Federica Moraca , Donatella Bagetta , Annalisa Maruca EMAIL logo , Francesca Alessandra Ambrosio , Roberta Rocca , Raffaella Catalano , Isabella Romeo , Carmine Talarico , Francesco Ortuso , Anna Artese und Stefano Alcaro
Veröffentlicht/Copyright: 8. Mai 2019
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Abstract

This paper focuses on advanced computational techniques for identifying and optimizing lead molecules, such as metadynamics and a novel dynamic 3D pharmacophore analysis method called Dynophores. In this paper, the first application of the funnel metadynamics of the Berberine binding to G-quadruplex DNA is depicted, disclosing hints for drug design, in particular clarifying water’s role and suggesting the design of derivatives able to replace the solvent-mediated interactions between ligand and DNA to achieve more potent and selective activity. Secondly, the novel dynamic pharmacophore approach is an extension of the classic 3D pharmacophores, with statistical and sequential information about the conformational flexibility of a molecular system derived from molecular dynamics (MD) simulations.

Acknowledgements

This work was partially supported by Dr. Giosuè Costa. The authors also gratefully acknowledge the helpful comments and suggestions of the reviewers, which have improved the presentation.

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Published Online: 2019-05-08

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