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Dr. habil. Agnieszka A. Kaczor

Research project


1. MSc project: Critical phenomena in 2D net-gas.

My MSc project involved application of computer simulation with Monte Carlo method to calculate critical exponents for 2D net-gas and to investigate critical phenomena in this system.

This project was awarded as the best project at the Faculty of Chemistry of UMCS, Lublin in 2000.


2. Medical University of Lublin: entering project: Studies on the synthesis of novel analgesic compounds (2001-2006).

This project covered application of classical synthesis to obtain novel derivatives of imidazo[1,2-a]pyrimidines which had been designed to exert analgesic action through opioid receptors. This project successfully finished with preparation of 24 new compounds, including very unstable enamines, which had been synthesized at -40°C with TLC control. It turned out that the reaction course is temperature-dependent, thus Spartan Pro software was used to locate transition states for the condensation reaction. The performed calculations enabled further discussion of reaction mechanism and its kinetic or thermodynamic control.

This project was performed in collaboration with: prof. Kalevi Pihlaja and dr Jari Sinkkonen from University of Turku, Finland and prof. Zbigniew Karczmarzyk from Podlasie Academy, Siedlce, Poland.


3. Medical University of Lublin: PhD project: Synthesis and study on novel non-competitive antagonists of GluR5/6 receptors with expected neuroprotective and antiseizure activity (2005 - 2008).

The project involved synthesis and studies of indole derivatives. The compounds were the most active non-competitive antagonists of GluR5 (currently called GluK1) and the first non-competitive antagonists of GluR6 (currently called GluK2). An integral part of the studies was the construction of the GluR5 and the GluR6 models which were the first complete models of any ionotropic glutamate receptor. The novel allosteric binding site at GluR5/6 was proposed.

This project was funded by Polish Ministry of Science, grant number 405 021 31/1121. Computations were performed under framework of computational grant by Interdisciplinary Centre for Mathematical and Computational Modeling, Warsaw, Poland, grant numer G3-18.

This project was performed in collaboration with: prof. Kalevi Pihlaja and dr Jari Sinkkonen from University of Turku, Finland, prof. Zbigniew Karczmarzyk from Podlasie Academy, Siedlce, Poland and prof. Klaus Unverferth and dr Christiane Kronbach from Elbion Institute, Dresden, Germany.


4. Postdoctoral projects and collaborations with scientists from abroad

a. Identification of novel molecular targets for the treatment of schizophrenia and the design of potent antipsychotics (2009-2011), project performed in the group of prof. Manuel Pastor from GRIB/PRBB, Barcelona Spain

This computational project involved application of homology modeling, docking (including protein-protein docking), molecular dynamics and virtual screening to elaborate novel treatments of schizophrenia.

b. Application of fractal theory to description of structure and function of proteins (2009-present), project started in the group of prof. Manuel Pastor from GRIB/PRBB, Barcelona Spain and continued in the group of prof. Antti Poso from University of Eastern Finland, Kuopio, Finland.

This project involves application of the fractal dimension as a measure of surface roughness to describe structural and functional features and to identify binding sites of G protein-coupled receptors, the complex of survivin-CDK4 kinase and proteins interacting with porphyrins.

c. Assessment of protein-protein docking tools for modeling complexes of transmembrane proteins (2009-2011), project performed in the group of prof. Manuel Pastor from GRIB/PRBB, Barcelona Spain.

The project involves extensive testing of protein-protein docking software for modeling complexes of transmembrane proteins, in particular G protein-coupled receptors.

d. Elaboration of multi-component protocol for modeling dimers of G protein-coupled receptors (2009-present); project started in the group of prof. Manuel Pastor from GRIB/PRBB, Barcelona Spain and continued in the group of prof. Stefan Dove from University of Regensburg, Germany and prof. Antti Poso from University of Eastern Finland, Kuopio, Finland.

e. Molecular modeling of D2R-mGluR5 heterodimer as a drug target in schizophrenia (2011-2012); project performed in the group of prof. Stefan Dove from University of Regensburg, Germany

The project involved application of homology modeling, protein-protein docking based protocol, molecular dynamics and structure-based drug design techniques to model D2R-mGluR5 heterodimer in different conformational states in order to design potent antypsychotics.

f. Molecular modeling of cannabinoid CB1 receptor homodimer and its interaction with ligands: the role of CRIP1a protein as well as modeling of other drug targets in the cannabinoid system (2012-present); project performed in the group of prof. Antti Poso from University of Eastern Finland, Kuopio, Finland.

The general aim of the project is to investigate in silico the phenomenon of the homodimerization of the CB1R, the interaction of the CB1R homodimer with ligands, including newly designed ligands, and to study the effect of membrane cholesterol and the CRIP1a on the functioning of the CB1R homodimer. The project is intended to verify a set of hypotheses on the functioning of the CB1R monomer and homodimer: (i) homodimerization of the CB1R is agonist-mediated (ii) the interface transmits the cross-talk between protomers in the CB1R dimer (iii) cholesterol promotes the CB1R homodimerization; (iv) cholesterol stabilizes the inactive state of the CB1R homodimer; (v) the CRIP1a stabilizes the inactive state of the CB1R monomer; (vi) the CRIP1a hampers the CB1R homodimerization.

g. Molecular modeling for the cannabinoid system (2012-present); project performed in the group of prof. Antti Poso from University of Eastern Finland, Kuopio, Finland.

The project involves modeling cannabinoid system enzymes (like MGL) and their interactions with inhibitors.

h. Molecular modeling of dimers of other GPCRs and their interaction with bivalent and allosteric ligands (2012-present)

The project focuses on histamine H4 receptor homodimer (collaboration with prof. Armin Buschauer and dr Oksana Sereda from University of Regensburg, Germany) and dopamine D2 receptor homodimer (collaboration with prof. Ben Capuano and dr Manuela Jörg from Monash University, Parkville, Australia).



  
About

Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Poland

Google Scholar: Agnieszka A. Kaczor
Researcher ID: A-3744-2015
Orcid: 0000-0001-8679-9623


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