A5000858314- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Trypanosoma species research and implications
- Tuberculosis Research and Epidemiology
- Cancer therapeutics and mechanisms
- Synthesis and Biological Evaluation
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- HIV/AIDS drug development and treatment
- Global Public Health Policies and Epidemiology
- Lipid Membrane Structure and Behavior
- Synthesis and Characterization of Heterocyclic Compounds
- Mass Spectrometry Techniques and Applications
- Genomics and Phylogenetic Studies
- Global Healthcare and Medical Tourism
- Research on Leishmaniasis Studies
- Click Chemistry and Applications
- Enzyme function and inhibition
- Bacteriophages and microbial interactions
- Synthesis and biological activity
University of Warsaw
2010-2025
Heidelberg Institute for Theoretical Studies
2016-2025
Heidelberg University
2019
Centrum Kopernika Badań Interdyscyplinarnych
2012
University of Virginia
2010
The TRAnsient Pockets in Proteins (TRAPP) webserver provides an automated workflow that allows users to explore the dynamics of a protein binding site and detect pockets or sub-pockets may transiently open due internal motion. These transient cryptic be interest design optimization small molecular inhibitors for target interest. TRAPP consists following three modules: (i) structure- generation ensemble structures using one more four possible simulation methods; (ii) analysis-superposition...
Abstract Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory function. MtFAS generates the octanoic precursor lipoic synthesis, but role of longer products has remained unclear. The structurally well-characterized component mtFAS, human 2E -enoyl-ACP reductase (MECR) rescues growth and lipoylation defects a Saccharomyces cerevisiae Δ etr1 strain lacking native mtFAS enoyl reductase. To address we employed in silico molecular simulations to design MECR variant with...
Pteridine reductase 1 (PTR1) is a key folate pathway enzyme of pathogenic trypanosomatids that reduces biopterin to dihydro- and tetrahydrobiopterin. It promising target for drug design against diseases such as sleeping sickness or leishmaniases. Amongst known PTR1 inhibitors, 2-aminobenzothiazole derivatives the pocket were previously found show good overall toxicity profiles some them display anti-parasite activity. On other hand, compounds containing 3,4-dichlorophenyl moiety,...
Structure-guided design is one of the most validated solutions for targeting proteins with specific ligands therapeutic purposes. Nevertheless, it remains challenging to target enzymes low affinity their natural and specificities that overlap those other proteins. Cytosolic 5'-nucleotidases - involved in metabolism nucleic acid derivatives are an example such a family. Here we illustrate how precisely designed covalent inhibitors represent potential solution selective nucleotidase targeting....
The conformational properties of the aminoacyl-tRNA binding site (A-site), and its surroundings in Escherichia coli 30S ribosomal subunit, are great relevance designing antibacterial agents. subunit A-site is near protein S12, which neighbors helices h27 H69; this latter helix, 50S a functionally important component an intersubunit bridge. Experimental work has shown that specific point mutations S12 (K42A, R53A) yield hyper-accurate ribosomes, turn confers resistance to antibiotic...
The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present systematic, multidisciplinary approach to development selective antiparasitic compounds. Computational fragment-based design novel pteridine derivatives along iterations crystallographic structure determination allowed for derivation structure–activity relationship multitarget inhibition. yielded showing apparent picomolar inhibition T. brucei reductase 1...
According to the World Health Organization, more than 1 billion people are at risk of or affected by neglected tropical diseases. Examples such diseases include trypanosomiasis, which causes sleeping sickness; leishmaniasis; and Chagas disease, all prevalent in Africa, South America, India. Our aim within New Medicines for Trypanosomatidic Infections project was use (1) synthetic natural product libraries, (2) screening, (3) a preclinical absorption, distribution, metabolism,...
By hindering or "silencing" protein translation in vivo, antisense nucleic acid analogues that hybridize to bacterial rRNA could serve as a promising class of antibacterial compounds. Thus, we performed comparative analysis the dynamical properties modified oligonucleotides based upon sequence 5′r(UGUUACGACU)3′ is complementary ribosomal A-site RNA. In particular, 25 ns explicit solvent molecular dynamics simulations were computed for following six single-stranded decamers: (1) above RNA...
There is a need for improved and generally applicable scoring functions fragment-based approaches to ligand design. Here, we evaluate the performance of computationally efficient model inhibitory activity estimation, which composed only multipole electrostatic energy dispersion terms that approximate long-range ab initio quantum mechanical interaction energies. We find computed energies correlate well with compound series varying substituents targeting two subpockets binding site Trypanosoma...
The mRNA decoding site (A-site) in the small ribosomal subunit controls fidelity of translation process. Here, using molecular dynamics simulations and bioinformatic analyses, we investigated structural human mitochondrial A-site (native A1490G mutant) compared it with bacterial A-site. We detected characterized a specific RNA backbone configuration, S-turn2, which occurs but not Mitochondrial A-sites show different propensities to form S-turn2 that may be caused by base-pairing patterns...
Views Icon Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Twitter Facebook Reddit LinkedIn Tools Reprints and Permissions Cite Search Site Citation Joanna Panecka, Trylska; Molecular dynamics techniques in the studies of bacterial ribosome. AIP Conf. Proc. 22 June 2012; 1456 (1): 207–214. https://doi.org/10.1063/1.4730661 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Dropdown...
Cytosolic nucleotidases (cNs) catalyze dephosphorylation of nucleoside 5'-monophosphates and thereby contribute to the regulation nucleotide levels in cells. cNs have also been shown dephosphorylate several therapeutically relevant analogues. cN-IIIB has vitro a distinctive activity towards 7-mehtylguanosine monophosphate (m7GMP), which is one key metabolites mRNA cap. Consequently, it proposed that participates cap turnover prevents undesired accumulation salvage m7GMP. Here, we sought...
The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present systematic, multidisciplinary approach to development selective anti-parasitic compounds. Computational fragment-based design novel pteridine derivatives along iterations crystallographic structure determination allowed for derivation structure-activity relationship multitarget inhibition. yielded showing apparent picomolar inhibition T. brucei reductase 1...
The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present systematic, multidisciplinary approach to development selective anti-parasitic compounds. Computational fragment-based design novel pteridine derivatives along iterations crystallographic structure determination allowed for derivation structure-activity relationship multitarget inhibition. yielded showing subnanomolar inhibition T. brucei reductase 1...
The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present systematic, multidisciplinary approach to development selective anti-parasitic compounds. Computational fragment-based design novel pteridine derivatives along iterations crystallographic structure determination allowed for derivation structure-activity relationship multitarget inhibition. yielded showing picomolar inhibition T. brucei reductase 1 (PTR1),...
The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present systematic, multidisciplinary approach to development selective anti-parasitic compounds. Computational fragment-based design novel pteridine derivatives along iterations crystallographic structure determination allowed for derivation structure-activity relationship multitarget inhibition. yielded showing picomolar inhibition T. brucei reductase 1 (PTR1),...