Further Insights in the Binding Mode of Selective Inhibitors to Human PDE4D Enzyme Combining Docking and Molecular Dynamics.

ABSTRACT: Alzheimer's disease has recently emerged as a possible field of application for PDE4D inhibitors (PDE4DIs). The great structure similarity among the various PDE4 isoforms and, furthermore, the lack of the full length crystal structure of the enzyme, impaired the rational design of new selective PDE4DIs. In this paper, with the aim of exploring new insights into the PDE4D binding, we tackled the problem by performing a computational study based on docking simulations combined with molecular dynamics (D-MD). Our work uniquely identified the binding mode and the key residues involved in the interaction with a number of in-house catechol iminoether derivatives, acting as PDE4DIs. Moreover, the new binding mode was tested using a series of analogues previously reported by us and it was used to

SUBMITTER: D'Ursi P 

PROVIDER: S-EPMC5094559 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature