Antonios Kolocouris earned his Bachelor's degree in Chemistry with honors in 1989 from the National and Kapodistrian University of Athens (NKUA). He completed his Ph.D. at the same university in 1995. From 1997 to 2000, he conducted postdoctoral research at the Institute of Chemical Biology, focusing on the application of NMR spectroscopy, molecular dynamics (MD) simulations, and other biophysical methods to study the conformation of peptides and other biomolecules.
In 2000, he joined the Department of Pharmacy at NKUA as a Lecturer. He was promoted to Professor of Medicinal Chemistry in 2020. His current research activities encompass the following:
1. Medicinal Chemistry / Computational Biochemistry
- Study of membrane protein ˗ ligand interactions, using computational-aided drug design (CADD): all-atom MD (AA MD) simulations, free energy calculations (ΜΜ-PBSA, FEP/MD, TI/MD); and biophysical methods (e.g., ΝΜR spectroscopy, DSC).
- Virtual screening of chemical libraries using structure- and ligand-based methods.
- Structure-activity relationships and 3D QSAR.
- Chemical synthesis of bioactive ligands.
Research Areas
- Influenza A Μ2 protein:
Studies of the interactions of aminoadamantanes with influenza A Μ2 constructs, M2(22-46) or M2(22-62) using:
(a) ΝΜR spectroscopy, ΙΤC, electrophysiology, antiviral assays in amantadine-resistant viruses, and
(b) MD simulations, binding free energy calculations using FEP/MD, ΤΙ/ΜD (2002–today). - Application of CADD methods and synthesis of aminoadamantanes and conjugates with polar head heterocycles against influenza A wild-type and amantadine-resistant strains S31N, V27A, L27F, G34E, A30T (2010–today).
- Adenosine receptors (ARs):
Virtual screening of chemical libraries; optimization of hits to leads using TI/MD calculations, synthesis of new selective antagonist derivatives based on chemical probes identified from virtual screening against ARs; ML-based models for prediction of ligands potency. - CADD and development of antagonists against A1R, A3R using MD simulations and TI/MD calculations as well as mutagenesis experiments (2019–today).
- Mmpl3:
This protein is a transporter of trehalose monomycolate (TMM) of Mtb, and we have designed computationally and developed new analogs of the drug SQ109, which is in phase II clinical trials against Mtb, using structure-based drug design. Strikingly, we found SQ109 analogs that are active against other pathogens including malaria, M. abscessus, and gram-negative bacteria (2018–today). - CB2R: We are developing ligands (CADD, synthesis) against CB2R (2021–today).
- P2X7R: For P2X7 purinergic receptors, we are running CADD for synthesis of antagonists using in the first cryo-EM structure of human P2X7 and orthologs.
- sEH:
We design and develop new inhibitors of soluble epoxide hydrolase enzyme; ML-based models for prediction of ligands potency (2021–today). - AT1R: Design and development of fluorescent probes (2024–today).
- Viral Mpro/PLpro:
We are working with inhibition of Mpro or PLpro from SARS-COV-2 or enteroviruses (2020–today). - Theranostics:
Design and development of new bioconjugate ligands against PSMA and GRPR (2020–today). - Conformational analysis of hydrophobic peptides:
MD simulations and DFT calculations are performed to examine the stabilization factors, e.g., N-H/O and C-H/O hydrogen bonds (2012–today). - Conformational analysis of AngII and AT1 antagonists:
MD simulations and NOE experiments were applied (1997–2000).
2. Biophysics
- Experimental biophysics (ssNMR, SAXS, DSC), AA MD, and coarse-grained MD simulations to investigate lipophilic drugs and membrane proteins interacting with membranes.
Research Areas
- We are running several biophysics experiments in combination with ssNMR experiments, and we are exploring the effect of lipids in M2 contribution in viral budding using coarse-grained (CG MD) MD simulations (2017–today).
- We are exploring the effect of SQ109 in membranes with experimental and computational methods (AA and CG MD simulations) and the transport mechanism of TMM by MmpL3 and its inhibition by SQ109 using CG MD simulations (2023–today).
- We are running CG MD simulations to study interactions between GPCRs and lipids (2021–today).
3. Physical - Organic Chemistry
- Dynamic NMR.
- Computational organic chemistry.
Research Areas
- Conformational analysis of organic molecules in solution using Dynamic NMR and molecular mechanics or quantum mechanical calculations (1995–2015).
- Weak intramolecular interactions:
Non-conventional hydrogen bonding C-H---X (X=O, N, F, S) in organic molecules using NMR chemical shift changes, and QM calculations of interactions and chemical shift changes (2005–today). - Non-conventional hydrogen bonding in lipophilic peptides and its effect on the folding using MD simulations, QM calculations, and experimental studies of folding (2010–today).
- Mechanisms of Au-catalyzed organic reactions using DFT calculations (2014–today).
- Evaluation of the accuracy of force fields and quantum mechanical methods and generation of databases for the conformational analysis of organic molecules (2017–today).
Editorial Board in International Journals
- Editorial advisory board of ACS Pharmacology & Translational Science (2021–today).
- Editorial advisory board of Frontiers in Chemical Biology (2023–today).
Additional Contributions
Antonios Kolocouris has authored numerous scientific journal articles and contributed to the writing of two significant books:
- A chemistry textbook for senior high school students.
- A comprehensive guide on computational chemistry and molecular simulations, providing detailed insights into the field.
