Modeling Epac1 interactions with the allosteric inhibitor AM-001 by co-solvent molecular dynamics.

ABSTRACT: The exchange proteins activated by cAMP (EPAC) are implicated in a large variety of physiological processes and they are considered as promising targets for a wide range of therapeutic applications. Several recent reports provided evidence for the therapeutic effectiveness of the inhibiting EPAC1 activity cardiac diseases. In that context, we recently characterized a selective EPAC1 antagonist named AM-001. This compound was featured by a non-competitive mechanism of action but the localization of its allosteric site to EPAC1 structure has yet to be investigated. Therefore, we performed cosolvent molecular dynamics with the aim to identify a suitable allosteric binding site. Then, the docking and molecular dynamics were used to determine the binding of the AM-001 to the regions highlighted

SUBMITTER: Bufano M 

PROVIDER: S-EPMC7533256 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature