Mikros group: Biomolecular Spectroscopy & Computational Drug Design Group

Address

Keywords

Drug design, Virtual screening, Molecular Simulation, NMR, Metabolomics, Hit to lead optimization

Models

Epigenetic targets (bromodomains, UHRF) Kinases (CDKs, GSK3, DYRK, CK1), Nuclear Receptors (ERα, ERβ, AR) membrane transporters (UapA, XanQ).

Techniques

Docking-scoring, Molecular Dynamics, Consensus scoring, FEP calculations, Solvent Mapping, (softwares: Schroedinger Suite, Desmond, AMBER, OPENEYE (ROCS, SZMAP). NMR and MS based Metabolomics (NMR 400 and 600 MHz, Orbitrap MS, Supercritical Fluid Chromatography MS (SFC-MS) Countercurrent Partition Chromatograph (CPC) software: Topspin, AMIX, MatLAb, SIMCA, Metaboanalyst)

Collaborations outside COST

Nothing

Short description of ongoing research projects

Our research is focused on NMR spectroscopy, NMR based Metabolomics Structure elucidation of biomolecules, natural products and drugs, as well as Structure Based Drug Design, Molecular Simulations, in silico screening and Structure Activity Relationships. Specific calculation protocols have been established and used in order to design new molecules with desired biological activity. Important experience has been gained through the systematic study of receptors like Kinases (CDKs, GSK3, DYRK, CK1), Nuclear Receptors (ERα, ERβ, AR), Epigenetic targets (bromodomains, UHRF) and membrane transporters. The group is also involved in several metabolomic projects covering areas like characterization of metabolic responses to chemical exposure (hepatotoxicity, cardiotoxicity), Functional genomics (NRF2) disease diagnosis (inborn error of metabolism, cancer), sports biochemistry and plant metabolic profiling.

Publications

1. Byrne B. et al Nature Communications 2016 Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity.
2. Myrianthopoulos V et al J. Med. Chem., 2016, 59 8787–8803) Discovery and optimization of a selective ligand for the Switch/Sucrose Non-Fermenting-related bromodomains of Polybromo protein-1 by the use of virtual screening and hydration analysis.
3. Myrianthopoulos V. et al Eur. J. Med Chem. 2016, 114, 390-396 Tandem virtual screening targeting the SRA domain of UHRF1 identifies a novel chemical tool modulating DNA methylation.
4. Petrakis TG et al Seminars in Cancer Biology 2016, 37-38 , 3–15 Exploring and exploiting the systemic effects of deregulated replication licensing
5. Tsakiri etal Journal Antioxidants and Redox Signaling 2017, in press The indirubin derivative 6-Bromoindirubin-3-oxime (6BIO) activates proteostatic modules, reprograms cellular bioenergetics pathways and exerts anti-aging effects

Other activities of potential interest to others