Selective targeting of muscular AMPK by structure based virtual screening

M. Miglianico, I.W.M. Bleylevens, G.A.F. Nicolaes, D. Neumann

Research output: Contribution to conferenceAbstractAcademic

Abstract

The energy-sensor AMP-activated protein kinase (AMPK) cycles between a glycogen-bound and a free state. The muscle-specific regulatory AMPKβ2 subunit carries a high affinity carbohydrate-binding module (CBM). Upon energy stress, such as exercise, AMPK localization at glycogen allows for rapid inhibition of glycogen synthesis, whereas cytosolic AMPK is capable of stimulating insulin-independent glucose uptake. By inhibition of glycogen-binding of muscular AMPK, we hypothesize to promote glycogen synthesis and glucose import, both of which are desirable processes for type 2 diabetes patients. Based on X-ray structures of AMPKβ1 and β2 CBMs, we performed a structure-based virtual ligand screen, using an established protocol that combines rigid and flexible docking. From a commercial 800,000 ligand database, we selected the best scoring 870 compounds after our in silico screen. These compounds show 81% isoform specificity and are currently being tested in vitro.
Original languageEnglish
Publication statusPublished - 1 Jan 2012
EventConference of Netherlands Society on Biomolecular Modelling (NSBM) and Netherlands Bioinformatics Centre (NBIC) -
Duration: 25 Apr 201225 Apr 2012

Conference

ConferenceConference of Netherlands Society on Biomolecular Modelling (NSBM) and Netherlands Bioinformatics Centre (NBIC)
Period25/04/1225/04/12

Cite this

Miglianico, M., Bleylevens, I. W. M., Nicolaes, G. A. F., & Neumann, D. (2012). Selective targeting of muscular AMPK by structure based virtual screening. Abstract from Conference of Netherlands Society on Biomolecular Modelling (NSBM) and Netherlands Bioinformatics Centre (NBIC), .